Ménière’s disease research

Current activity
Acoustics Australia Special April 2006 Edition Reviewing Mechanisms, edited by E.LePage

This project was undertaken at the invitation of Prof. Joe Wolfe, senior editor of Acoustics Australia. This is a refereed journal issued 3 times a year and features special topics from time to time. This edition (Vol. 34, No. 1) is directed at the mechanisms of hearing and response to trauma. As invited guest editor, I saw the opportunity to produce a series of short review articles about the current status of auditory mechanisms, and I invited noted Australian investigators to participate.

The result contains seven articles. The seven first authors are Pickles, Irvine, Mulders, Carlile, Dahl, Sen and LePage. All articles were reviewed by at least two reviewers, for the most part senior investigators. The resulting contributions cover wide-ranging topics from spatial perception, plasticity in the cortex, efferent control, genetics, potassium recycling, mitochondrial energy underpinning of many cochlear processes, a modeling account of two-tone suppression and upward spread of masking. It also reviews direct cochlear mechanical measurements in which the objectives have had as much to do with cochlear homeostasis as cochlear tuning. Although primarily reviews, quite a few new ideas have been developed which should be of as much interest to those working on the etiology of Ménière’s disease or noise-induced hearing loss, as to those studying tuning mechanisms.

The final article in this special edition specifically looks at a model which proposes that hydrostatic pressure variations in scala media are a normal part of cochlear function which accounts for the changes in gain of the cochlear amplifier via a bias effect which depends upon sound level. Hydrops therefore is not an abnormal condition, per se, but when it is so advanced it causes rupture of the vessel is leads to the attacks of vertigo. There are many potential explanations for well-described cochlear phenomena via this approach.

The Australian Acoustical Society is making further copies of this 60 page edition available at cost (approximately USD20.00 which covers printing and airmail). Please go to Mechanisms of Hearing Damage for contents, abstracts and ordering.

Compiled works on direct mechanical measurements

NEW! For those wishing to delve deeper into the long history of progress towards this model, I have compiled a series of my publications over the past 25 years. The idea that hydrostatic pressure is an important component of signal processing was first advanced in my doctoral dissertation (1981) contained in this compilation in full. The subsequent publications evaluated by direct mechanical measurement baseline shifts in the position of the basilar membrane which became very controversial, since they could not be duplicated in the basal turn. Yet in terms of the new model, these baseline shifts are appreciated as not being strongly evident in high sensitivity preparations and so were missed. Their revelation did not require highly sophisticated laser interferometry so much as a different hypothesis. Another important factor may have been the ease of using my sensors, both of which were supported in a standard micromanipulator and were as easy to maneuver as a glass micropipette. The key reason these baseline shifts have been so elusive seems to be best explained in terms of a servo-loop. Only in preparations which externally applied biases affect the operating point of the outer hair cells, will these baseline shifts be observed. Low thresholds and sharp tuning may be sufficient reason not to see them. The whole story unfolds in The Mechanics of Cochlear Homeostasis.

Conference presentation

Presentation for 5th International Symposium on Ménière’s Disease & Inner Ear Homeostasis Disorders 2 – 5 April, 2005. (This is a large file 807kB of the powerpoint handout).

This work presents a novel approach to otoacoustic measurement. To most people “otoacoustic emissions” means just that….. sounds coming out of the ear; the sounds being referred to as audible sounds or at least sounds measurable with a microphone in the ear canal. The generic term “OAE” carries the implicit assumption that sounds are emitted and that they are within the auditory passband, i.e. 20 Hz to 20 kHz. This may be partly because of a historic mindset that because the inner ear encodes sounds within the auditory passband, that all cochlear processing also occurs within the auditory passband. While the mathematical modellers are still wrestling with the difficulties of integrating homeostatic processes into their models, cochlear physiologists have known almost since earliest days, that the cochlea functions down to “dc”, that is, zero frequency. Very slow homeostatic processes are involved in regulation of hearing sensitivity and internal protection mechanisms, to noise and other toxic influences. The other reason that homeostatic processes have been difficult to deal with is that they have very long time courses, much longer than the auditory signals often used as stimuli, with the consequence that hearing measures are very often not reproducible in the short term. By and large, practitioners in clinical hearing science have ignored the non-reproducible behaviour – it is added to the “too-hard” basket. Indeed even the making of internal physiological measurements and external otoacoustic emission measurements are plagued by issues of variability beyond experimental control, at least for simple experimental questions. In general, evoked otoacoustic emissions have large, labile and generally bad behaviour less than 500 Hz, and for this reason all commercial OAE equipment filters it out. Two thousand plus OAE studies published mostly have ignored all the behaviour which we now recognise as homeostatic influence, partly middle ear in origin, and as we show by this novel approach certainly with behaviour which is unambiguously cochlear in origin. We have “grasped the nettle” as it were and set out to see if meaningful results can be obtained, closer to traditional cochlear physiological description, without presuming that in order to get it out through the middle ear, it must be within the auditory passband. Recently Sirjani, Salt and colleages have examined the quadratic difference component and made meaningful estimations of outer hair cell operating points, deriving from very low frequencies; which has suggested that one doesn’t need to presume the response exists at the frequency f2-f1 at all. A patent application has been submitted for this new approach.

History of Interest

Ménière’s disease is a syndrome comprised of a clutch of symptoms surrounding hearing loss and tinnitus, but the most telling of which are attacks of vertigo and nausea which are strongly disabling. Not all of the symptoms are necessarily present at any one time. Morphologically these attacks are associated with abnormal pressure buildup in scala media and the endocochlear duct. The mechanisms behind these symptoms have remain elusive for many years. It used to be thought that endolymph was produced in the cochlea, and this results in a small flow towards the endolymphatic sac. Accordingly, there has tended to be a focus on surgical procedures upon the endolymphatic sac designed to relieve pressure buildup in the endolymph. In more recent times, Alec Salt has shown that there is no good evidence for such a flow. Instead, attention is being focussed upon cochlear mechanisms and this is driven by the knowledge that the cochlear is not just a passive transducer, but an active transducer. Sound modulates the currents through the outer hair cells so that homeostasis constitutes a major subfunction of the cochlea. Alec recently spoke to the 25th annual meeting of the NSW Meniere’s Support Group and gave a graphic account of the complexity not just of teasing out the mechanisms, but even explaining the nature of the research to fellow hearing professionals.

My interest in the area stems from the very first set of experiments did as a masters student in Brian Johnstone’s laboratory in the Physiology Department at the University of Western Australia. I was making direct measurements of the motion of the basilar membrane in the cochleas of guinea pigs. My Masters project was to control the motion to be simple mathematical functions such as triangle waves or trapezoidal waves (LePage and Johnstone, 1975). Having achieved this we have a simpler mechanical input to the hair cells of the cochlea. The unexpected difficulty arose that the motion was not just “ac”, but possessed a substantial “dc” component as well in which I monitored large changes in the position of the basilar membrane, such as has been shown due to pressures building up in the cochlea. While such “dc-shifts” were certainly artifactual from a signal processing point of view, the consideration of this class of membrane movement has become vital when characterising pathological conditions in hydrops, or the buildup of pressure in scala media. It has been clear during the 15 years of clinical work on otoacoustic emissions in humans, that emissions are indeed sensitive indicators of baseline movement, so much so, that for most clinical measurements, all low frequency emission components are summarily filtered out because of their complexity. I have always strongly been interested to explore the role of low-frequency components of basilar membrane motion using otoacoustic emissions and I had the opportunity to tell of that interest in an invited talk to the Meniere’s Support Group of Victoria, Australia in 1999.

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