Von der Nano-Mechanik des Hörens zum modernen Hörgerät Stefan Launer, Sonova / Phonak AG, Senior Vice President Science & Technology Adjunct Professor Univ. of Queensland, Brisbane 1
Content Physiology, anatomy Nano-Mechanics of inner ear Inner hair cells sensor Outer hair cells motor Sensorineural hearing loss Hidden hearing loss 2
Makro-. Nanowelten 3
Auditory Pathway - Mammals 5
Macro-mechanical vibration in cochlea Geisler Bild 5.1 S. 56 7
Macro-mechanical vibration - simplified model 8
Vibration of the Organ of Corti IHC: Sensor OHC: Motor 0.3 nm 9
Mearsured basilar membrane input/output characteristic: it is compressive! 10
Nanomechanics at work, brownian motion is larger Lagrade et al Nature Neuroscience 2008 11
Mechano-electrical transduction 13
Inner Hair Cell - Structure IHC Soma length: 40-50 um IHC Cilia length: 4-5 um Cilia diam.: 0.5 um 50 80 ciliae per hair cell Length of tip link: 170 nm, width 5 nm 15
Nanomechanics, complex nano-structure Vollrath, Corey, Annual Review Neuroscience 2007; Kazmierzack and Müller 2012, T in Neuroscience 2012 16
Channel opening: fast and slow adaptation Kazmierzack and Müller 2012, T in Neuroscience 2012 Nonlinear (negative) stiffness of hair bundles, hair bundle motility 17
Gating Mechanisms Christen and Corey, Nature Neuroscience Reviews 2007 18
Synchronous Stereocilia Movement (2007/2008) Serial Arrangement Parallel Arrangement - larger excitation 21
Coupling of hair bundles Hair bundles are not only locally coupled via the tip links but also with their neighbors via via the mechanical structure and the viscoelastic coupling coherence accross various hair bundles reduces threshold and compensates for noise floor 22
MECHANICAL Transduction channel Ca2+ channel, resting potential -60-80 mv Direct mechanical gating very fast response time, 10-20 usec Opening of transduction channel: 2-4 nm, Force: 10 pn Open probability: 50 %? lowering threshold?! Coupling within and accross hair cells lowering threshold, noise floor 2 channels per stereocilium? Non-linear gating stiffness Fast and slow adaptation of channel Channel conductance varies accross length of cochlea 24
Length Change um OHC Motility: Length Change (1985) Potential mv 25
Äussere Haarzellen bewegen sich 26
OHC - Active Process bloody fast (1999) Bats: hearing up to 100 khz! Over life time 27
Prestin presto (fast.) (2000) 28
Active Outer Hair Cell Mechanics: two processes?! 29
Nanomechanic - active processes Large dynamic range Large spectral resolution Low threshold Otoacoustic emissionen diagnostics 30
Sensorineural Hearing Loss 31
April 2016 Process of Hair Cell Apoptosis due to Acoustic Trauma Three different sites of lesion, depending on etiology of hearing loss, exist: Sensory: Damage to hair cells Neural: damage to auditory neurons and synapsis Homeostasis: damage to energy supply to inner ear Age related hearing loss (most common form): combination of different etiologies, i.e. most complex form of hearing loss Page 32
New paradigm of physiological origin of sensorineural hearing loss? Current hypothesis: physiological origin of sensorineural hearing loss is damage to inner and outer hair cells S. Kujawa, C. Liberman et al showed in a series of studies that we might have to re-think the way we think of the physiological origins hearing loss «hidden hearing loss» might exist (J Neuroscience 2009 & 2013, JARO 2011) Kujawa & Liberman, 2009, J Neuroscience Lin, Furman, Kujawa, Liberman 2011 Sergeyenko, Lall, Liberman, Kujawa 2013 34
Hidden Hearing Loss: Persistent Amplitude Declines Although thresholds recover, neural response amplitudes do not why? Kujawa & Liberman, 2009, J Neuroscience 35
Hidden Hearing Loss: Preserved Thresholds, Compromised Supra-Threshold Hearing Lin, Furman, Kujawa, Liberman 2011, JARO Single-fiber recordings show selective loss of low- and medium-sr fibers 36
REAL WORLD LAB. TASKS NEURAL Potential consequences of hidden hearing loss LOSS OF AUDITORY NERVE FIBRES modified after Plack 2014 INCREASE IN CENTRAL GAIN DEFICIT IN TEMPORAL CODING DEFICIT IN INTENSITY CODING POOR IPD DISCRIMINATION POOR FREQUENCY DISCRIMINATION POOR INTENSITY DISCRIMINATION Gestalt rules: Streaming or segragation of sound TINNITUS / HYPERACUSIS POOR SOUND LOCALISATION POOR SPEECH IDENTIFICATION IN SPATIAL NOISE POOR MUSICAL PITCH PERCEPTION 37
Perceptual Consequences of Hidden Hearing Loss Lopez-Poveda: a simple vocoder type model with multiple stochastic spike generators per frequency channel to simulate de-afferentiation Pre-processed speech sounds in quiet in noise with different hypothesis Normal/control N=300/band, slight deafferentiation N=10/band, strong deafferentiation Little difference for speech intelligibility in quiet Sound quality strongly degraded Significant and strong difference for speech intelligibility in noise Lopez-Poveda & Barrios 2013, Frontiers in Neuroscience, Vol 7 Lopez-Poveda 2014, Frontiers in Neuroscience, Vol 8 39
Hidden Hearing Loss: from the lab to the clinic Animals humans? Additional component to sensorineural hearing loss seems to exist hidden hearing loss Supra-threshold hearing loss Does not show up in audiogram Various etiologies: noise induced, aging, What are the perceptual consequences of such a hidden hearing loss? Psychoacoustic abilities? (Envelope perception: Stone & Moore 2008) Speech intelligibility / communication effort in complex environments? Which environments? How do we best diagnose and quantify hidden hearing loss? Basic psychoacoustic testing? Grouping rules from Auditory Scene Analysis work? Electrophysiological measures Speech testing? Environment? Attention, effort, memory Rehabilitation, devices? 40
Summary Hearing: Nanomechanics Exquiste mechanical properties, rather robust Open questions around details of molecular mechanical archtiecture Active processes Threshold sensitivity, dynamic range, freqeuncy resolution Physical limits Hearing impairement: different sites of lesion Hidden hearing loss 41
Merci! Danke!! 42
Fragen Was heisst NANOmechanik im Ohr? Wie gross bzw klein sind die Strukturen die sich im Ohr bewegen? Welche Schädigungen treten im Innenohr bei einer sensori-neuralen Schwerhörigkeit auf und welche Konsequenzen auf die Wahrnehmung hat eine solche Schädigung? Welche neueren Erkenntnisse zur Innenohrschwerhörigkeit erfordern ein Überdenken der klassischen Vorstellung zur Innenohrschwerhörigkeit? Welche Grenzen der klinischen Diagnostik ergeben sich dadurch? Was bedeuten diese Erkenntnisse für die klinische Praxis? Wie oft erlebt ihr es in der klinischen Praxis dass Personen beklagen in schwierigen Situationen schlecht zu verstehen aber ein normales Audiogram haben 43