TRFII-6

Inner ear homeostasis in vestibular disorders

Principle Investigators:

Dr. Markus Drexl, Ph.D.
Prof. Dr. Eike Krause, M.D.
Dr. Robert Gürkov, M.D.
Prof. Lutz Wiegrebe, Ph.D.

Objectives:

We are interested in the mechanisms underlying impairments in the homeostasis of the inner ear: Meniere’s Disease (MD) is a severe consequence of homeostatic inner-ear dysfunction. Our work has shown that low-frequency sound stimulation can transiently induce symptoms comparable to MD, resulting in a new tool to investigate the cause of MD and evaluating the effectiveness of treatment.

Project description:

Our research rests on two main pillars: human psycho- and biophysics (on patients and healthy subjects) and animal models. Our team has more than 15 years of experience with psychophysical methods in humans, including the measurement of masking period patterns, which is a well-established method in our lab. In addition, the team is one of few in the world to carry out experiments on the influence of very low-frequency sound on the human inner ear. LF tones have been repeatedly used to investigate cochlear function. Our group has shown that strong LF stimulation can interfere with cochlear homeostasis, manifesting in transient psychophysical and biophysical symptoms quite similar to MD. We could already show that low-frequency sound affects the generation of otoacoustic emissions in a very specific way which has the potential to be exploited for diagnostic purposes. We also comprehensively characterised the human Bounce phenomenon on the level of cochlear physiology and psychoacoustics and are therefore in an ideal position to transfer our experience with the phenomenon and with very low-frequency sound exposure to a level where it might serve as a temporary model for endolymphatic hydrops. Latest results of our team show that spontaneous otoacoustic emissions, a very sensitive product of active cochlear processes, show temporary and oscillating changes of frequency and level compatible with transient homeostatic changes and endolymphatic hydrops.

Bild1

Left: Free-field setup for the delivery of low-frequency sound and SOAE recording. Right: oscillations of level (a) and frequency (b) of SOAEs after presentation of the same low-frequency sound in the free-field.

 

The second pillar of our research are animal models: We have implemented and successfully published a whole series of experiments focusing on cochlear physiology. In particular, we have measured OAEs and auditory evoked potentials in animals as well as measures of cochlear mechanics. Experience with psychophysical methods in animals will enable us to characterise vestibular deficits of animal expressing endolymphatic hydrops whereas our electrophysiological expertise will allow us to dissect the events leading to impairments of cochlear homestasis.

 

Methods:

  • Low-frequency sound stimulation (both free-field and in-ear)
  • Biophysics and psychoacoustics of the auditory system
  • Galvanic stimulation of the mammalian inner ear (MCM-T)
  • Inner ear electrophysiology (MCM-T)

 

Relevant publications:

Kugler K, Wiegrebe L, Grothe B, Kössl M, Gürkov R, Krause E, Drexl M. Low-frequency sound affects active micromechanics in the human inner ear (2014). R. Soc. open sci. 2014 1 140166; DOI: 10.1098/rsos.140166.

Drexl M, Überfuhr M, Weddell TD, Wiegrebe L, Krause E, Gürkov R. Multiple indices of the Bounce phenomenon obtained from the same human ears (2014). J Assoc Res Otolaryngol. 15(1):57-72.

Drexl M, Lagarde MM, Zuo J, Lukashkin AN, Russell IJ (2008) The role of prestin in the generation of electrically evoked otoacoustic emissions in mice. J Neurophysiol 99:1607-1615.

Lagarde MMM*, Drexl M*, Lukashkin AN, Zuo J, Russell IJ (2008) Prestin's role in cochlear frequency tuning and transmission of mechanical responses to neural excitation. Current Biology 18:200-202. *joint first authors

Lagarde MMM*, Drexl M*, Lukashkina VA, Lukashkin AN, Russell IJ (2008) Outer hair cell somatic, not hair bundle, motility is the basis of the cochlear amplifier. Nature Neuroscience 11:746-748. *joint first authors

Siveke, I., C. Leibold, K. Kaiser, B. Grothe and L. Wiegrebe (2010).. Level-dependent latency shifts quantified through binaural processing. J Neurophysiol., 104: 2224-2235.

Siveke, I., S. D. Ewert, B. Grothe and L. Wiegrebe. 2008. Psychophysical and physiological evidence for fast binaural processing. J Neurosci, 28: 2043-2052.

 

Team:

speaker photo Marga_IFB Gürkov krause-neu
Lutz Wiegrebe   Markus Drexl  Margerete Überfuhr Robert Gürkov Eike Krause 

Contact:

Markus.drexl@med.uni-muenchen.de

Tel: + 49 (0) 89 2180 74340