Decreasing hair cell counts in aging humans.

Deterioration of balance with advancing age is a well-known fact of life. Some investigators have reported a 50% prevalence of dizziness in the elderly. Clinically, progressive dysequilibrium of aging presents as gradually worsening balance due to age-related decline in function of the peripheral vestibular system, central nervous system, vision, and musculoskeletal system. Vestibular function testing has shown clear evidence of age-related changes in peripheral and central sites. Histopathologic changes in the vestibular sensory organs include progressive hair cell degeneration, otoconial degeneration in the otolith organs, and decreasing number of Scarpa's ganglion neurons. Recently, a new quantitative method of assessing vestibular otopathology has been described, utilizing Nomarski differential interference contrast microscopy. This technique has been applied to 67 human temporal bones of individuals from birth to age 100 to create a normative database of total, type I, and type II hair cell counts as a function of age. Results show a highly significant continuous decrease in all counts from birth to age 100, best fit by a linear regression model. Type I hair cell counts in all three semicircular canal cristae decrease at a similar rate, significantly faster than the degeneration observed in type I hair cells of the maculae. Type II hair cell counts decline at the same rate for all 5 sensory epithelia. These normative data provide the basis for comparisons to hair cell counts made in temporal bones from subjects with known vestibular disorders. They also provide a basis for drawing correlations between vestibular function testing and vestibular otopathology.

Application of multivariate statistics to vestibular testing: discriminating between Menière's disease and migraine associated dizziness.

Menière's disease (MD) and migraine associated dizziness (MAD) are two disorders that can have similar symptomatologies, but differ vastly in treatment. Vestibular testing is sometimes used to help differentiate between these disorders, but the inefficiency of a human interpreter analyzing a multitude of variables independently decreases its utility. Our hypothesis was that we could objectively discriminate between patients with MD and those with MAD using select variables from the vestibular test battery. Sinusoidal harmonic acceleration test variables were reduced to three vestibulo-ocular reflex physiologic parameters: gain, time constant, and asymmetry. A combination of these parameters plus a measurement of reduced vestibular response from caloric testing allowed us to achieve a joint classification rate of 91%, independent quadratic classification algorithm. Data from posturography were not useful for this type of differentiation. Overall, our classification function can be used as an unbiased assistant to discriminate between MD and MAD and gave us insight into the pathophysiologic differences between the two disorders.

Multivariate vestibular testing: thresholds for bilateral Ménière's disease and aminoglycoside ototoxicity.

Although patient symptoms and an audiogram can typically identify the affected ear or ears in Ménière's disease, there are some cases where this differentiation is problematic. This paper concentrates on the sole use of vestibular test data to discriminate between unilateral and bilateral Ménière's disease. Patients that were known to have peripheral unilateral vestibular hypofunction (n = 104) were used as learning groups to define a region in multidimensional measurement space consisting of four vestibular test scores which summarized data from electronystagmography, sinusoidal harmonic acceleration, and computerized dynamic posturography tests. A multivariate boundary was created from the unilateral learning group that determined thresholds for identifying bilateral vestibular hypofunction. Patients with bilateral Ménière's disease (n = 23) and with bilateral ototoxicity (n = 19) were then used as test subjects to determine the sensitivity of the multivariate boundary. Results showed up to a increase in estimated test sensitivity (specificity = 95%) from 67%(current method)to 82%(new method)in identifying bilateral vestibular hypofunction.

Multivariate vestibular testing: laterality of unilateral Ménière's disease.

This paper discusses the use of vestibular testing to discriminate between right (n = 29) and left (n = 27) Ménière's disease. We examined reduced vestibular response (RVR), directional preponderance, and spontaneous and positional nystagmus measurements from electronystagmography, as well as the asymmetry measurements from the sinusoidal harmonic acceleration test, to determine whether multivariate logistic regression could improve upon the discrimination performance of RVR alone. We found that patients with a spontaneous or positional nystagmus often had a "recovery nystagmus", beating in the opposite direction of that predicted for an acute lesion. When present, the direction and magnitude of such nystagmus could be used in the classification algorithm to increase the discriminatory power over RVR alone, but in these patients the rotation test asymmetry measurements were rendered useless. In the absence of spontaneous or positional nystagmus, asymmetry measurements significantly enhanced right/left discrimination. Directional preponderance was insignificant in determining the side of lesion.

The human oculomotor response to simultaneous visual and physical movements at two different frequencies.

In order to investigate interactions in the visual and vestibular systems' oculomotor response to linear movement, we developed a two-frequency stimulation technique. Thirteen subjects lay on their backs and were oscillated sinusoidally along their z-axes at between 0.31 and 0.81 Hz. During the oscillation subjects viewed a large, high-contrast, visual pattern oscillating in the same direction as the physical motion but at a different, non-harmonically related frequency. The evoked eye movements were measured by video-oculography and spectrally analysed. We found significant signal level at the sum and difference frequencies as well as at other frequencies not present in either stimulus. The emergence of new frequencies indicates non-linear processing consistent with an agreement-detector system that have previously proposed.

Classification of human rotation test results using parametric modeling and multivariate statistics.

The usefulness of vestibular testing is directly related to the accuracy of the test interpretations. Two factors, subjective analysis of large test data sets and failure to make appropriate age corrections, tend to reduce test accuracy. Correction of these problems can be accomplished by application of physiologically based models of vestibular function and multivariate classification techniques to the test data, thereby creating a more objective test interpretation procedure. Herein we report our results on the use of this strategy for analysis of sinusoidal harmonic acceleration (SHA) test interpretation. For each patient, models reduce the large set of SHA test variables to three key parameters: asymptotic gain, vestibulo-ocular reflex time constant, and bias. In addition, the new technique objectively adjusts these parameters for the patient's age. Finally, each patient's set of parameters are statistically classified as either normal or as unilateral peripheral deficit. Based on learning sets of 57 normals and 30 patients with a full unilateral peripheral deficit, this new technique resulted in a misclassification rate between the categories of normal and full unilateral loss of 3.4%, comparing favorably to the present method's misclassification rate between normal and abnormal of 13.8%. We also analyzed and classified a test group consisting of patients with possible partial unilateral deficits using the same classification function as the normal and full unilateral learning sets. Even though the classifier was not optimized for the partial group, results seemed favorable relative to the human interpreter. These results validate the accuracy and utility of physiological parametric models and multivariate statistical classification in SHA test interpretation.

Stiffness of hair bundles in the chick cochlea.

The stiffness of hair bundles from isolated chick cochlear hair cells was measured in tissue culture medium. A water jet was used to deflect fiberglass fibers, quartz fibers, and hair bundles of isolated hair cells. A voltage-displacement curve was generated for a water jet ramp stimulus applied to miniature fiberglass and quartz fibers. Fiber displacements were measured using video image subtraction techniques. A force-voltage calibration curve was then derived for the fibers by modelling them as cantilever beams subjected to point forces at the tips. A voltage-displacement curve was then generated for isolated hair cell stereociliary bundles using the same procedure as for the fibers. A corresponding force-displacement curve was derived for isolated hair cells under water jet stimulation by correlating maximum ramp voltage from the hair cell's voltage-displacement curve to a corresponding force applied to a fiber from the fiberglass fiber calibration curve. The stiffness of the hair bundle, which is the slope of the hair cell's force-displacement curve, was then calculated using Hooke's law, assuming the force was distributed along the entire length of the hair bundle. The mean stiffness value was 5.04 +/- 2.68 x 10(-4) N/m for 14 hair cells, and was in close agreement with previously reported stiffness values of several investigators utilizing different animal models and procedures.