Processing of sounds in the inner ear Sripriya Ramamoorthy Associate Professor, IIT Bombay WiSSAP 2018
Cochlea converts sound into electrical signals [Picture courtesy of Northwestern University]
von Bekesy s theory of passive cochlea flexible plate of varying impedance (high at the base, low at apex) Basis for tonotopic separation of incoming frequencies
Cochlea has thousands of sensory cells Coiling direction AN https://hms.harvard.edu/news/splitting-hair-cells
Sensory cells can be damaged These fine sensory cells cannot be regenerated in mammals (but birds can) Cochlear sensory hair cell regeneration is a very hot research topic
Hearing Loss Exposure to loud noise Natural aging Genetic Head Injury Ototoxic medications Illness and infections
Hair cell regeneration Brigande & Heller 2009
Hearing aids
MEDEL Cochlear implants
Combined electric and acoustic hearing (Shorter) cochlear implant for high frequencies Hearing aid with residual hearing for low frequencies MEDEL An optimized and balanced control of electric and acoustic stimulation is necessary to obtain results superior to those achieved with hearing aids or conventional CIs.
Some practical challenges https://auditoryneuroscience.com/prosthetics/music https://auditoryneuroscience.com/prosthetics/noise_vocoded_speech
Cochlea vs. artificial speech processors Speech processors for cochlear implants MEDEL Cochlear signal processing is replaced by speech processors. 1 to 24 channels replace > 3000 channels in a cochlea Electrical stimulation is vastly inferior to acoustic hearing in spatial (tonotopic) resolution. [Shannon 2008] The task is made no easier by the fact that many basic aspects of normal hearing, for example the precise bases for loudness and pitch coding, are incompletely understood [Rubinstein 2004; Moore 2003]
Range of audibility of the human ear
Speech signal processing Speech signals are primarily processed in the apex
Base vs. Apex could be fundamentally different Auditory nerve and inner hair cells phase-lock at low-frequencies < 1000 Hz (apex) but do not phase-lock at high-frequencies > 1500 Hz (base) From A.R. Palmer (online) Intracellular receptor potentials recorded from an inner hair-cell in response to 80 db SPL tones Russell and Palmer, 1986
Phase locking The auditory nerve will tend to fire at a particular phase of a stimulating lowfrequency tone. With high frequency tones (> 3kHz) phase locking gets weaker, because the capacitance of inner hair cells prevents them from changing in voltage sufficiently rapidly. http://www.lifesci.sussex.ac.uk/home/chris_darwin/perception/lecture_notes/hearing2/hearing2.html
Measurement of frequency-tuning at Base vs. Apex Chinchilla apex vs. base Apical location Basal location From Robles and Ruggero, 2001
Active amplification Cochlea amplifies response to low sound levels Alive, low level Amplification Dallos & Fakler, 2002 Dead or high level Frequency
Compressive nonlinearity active gain passive Stimulus amplitude (db SPL) Johnstone et al (1986)
Otoacoustic emissions (OAE) ears not only process sound, but also emit sound Since their discovery in 1978 by David Kemp, it has been shown that the OAE originate inside the cochlea and propagate backwards to exit the ear. Details of how they originate and propagate inside the cochlea are currently hot research topics. speaker emits stimulating sound, microphone records returning OAE [picture taken from www.the-cochlea.info]
Electrically evoked sound reverse acoustic path along the middle and outer ear Portion of this picture is taken from the website: www.the-cochlea.info
Electromotility in outer hair cells https://auditoryneuroscience.com/ear/dancing_hair_cell
Electrical-structural coupling at outer hair cells HB OHC Mechano-electrical transduction [from www.the-cochlea.info] Electro-mechanical transduction [from W.E.Brownell s web-page]
Ionic fluids in the cochlea SV SM ST [from www.the-cochlea.info] SV,ST contain ionic fluid low in K+, high in Na+ SM contains ionic fluid high in K+, low in Na+. Its potential is almost 80 mv higher than SV,ST. Stria-Vascularis battery maintains the potential difference and powers the active process in a living animal.
Hypothesis for active feedback process Organ of Corti System-Level Sound waves Organ-Level Cellular-Level Outer Hair Cells Hair Bundles Molecular-Level
Active feedback loop Sound Stimulus Organ of Corti Vibration OHC applies active force due to motility Hair Bundle Deflection OHC Receptor Potential is modulated Potassium Ions enter the OHC
Health Applications Normal vs. impaired hearing Original After damage Speech processors for cochlear implants Mechanisms of normal and impaired hearing are poorly understood. Less than 24 channels replace > 3000 channels in a cochlea Cochlear signal processing is replaced by speech processors. MEDEL Non-invasive diagnosis of hearing (otoacoustic emission test) OAE can pin-point location and nature of inner ear damage. But, cochlear origin of OAE is not understood.
Multi-scale computational model of the cochlea
Model goals Predict how the cochlea responds to sound stimulation and electrical current stimulation Determine system-level changes arising out of cellular and molecular mechanisms in the cochlea Provide a platform for testing normal vs. abnormal hearing
Mechanical-Electrical-Acoustic Model of the Cochlea Ramamoorthy et al, 2007 Acoustic/Fluidic Electrical Structural
Two-duct fluid model Unwrapped Idealization apex L s 2 p z 2 p 2 c u ( p z f u z base Assumptions: inviscid and compressible fluid; fluid viscosity is lumped into structural damping p SV in SV,ST p ST ) on BM BM Fluid equations Fluidloading on BM Euler's relation at BM Ramamoorthy et al, 2007
Structural model Model schematic Structural anatomy TM BM RL OHC BM: Basilar Membrane TM: Tectorial Membrane RL: Reticular Lamina OHC: Outer Hair Cells 3 independent d.o.f. BM first beam-mode, TM bending mode, TM shear mode. Lagrange s method to derive governing equations. In addition to fluid pressure, active force is applied on the structures due to OHC piezo-motility. Ramamoorthy et al, 2007
Piezo-Electric Model of Outer Hair Cell Nonlinear force-current relationship: linearized in the model Force-Current constitutive relationship: Active force due to voltage-change F OHC k OHC u OHC d 31 OHC I OHC d 31 u OHC Y E OHC Current due to OHC vibration Ramamoorthy et al, 2007
Mechanical-electrical transduction at the hair bundles Scala Media Dc Voltage across= V 0 OHC Apex Animation by S.Blatrix G 0 G 1 Model linearizes change in conductance ( ac) G GV u I HB 0 1 0 Kirchhoff term HB Eqvt. to current source Ramamoorthy et al, 2007
Model for Electrical Network in the Cochlea OHC Applying Kirchoff s Law at four junctions leads to four governing equations. Two current sources from mechanical-electrical coupling drive this electrical network to produce cochlear-microphonic potentials. Changes in OHC potential generates active force (which is applied on adjacent structures) Ramamoorthy et al, 2007
Three-dimensional Finite Element Analysis K Q 0 p f F FS Q K Q u 0 SF S SE 0 Q K i ES E src Acoustic input p: fluid pressure u: structural displacements φ: electrical potentials Injected current used in animal expts Ramamoorthy et al, 2007
MEA model vs. Measurements in response to sound Vibrations Electrical potentials Ramamoorthy et al, 2007
Local electrical excitation of the cochlea MEA model experiment: Grosh et al (2004)
Summary for MEA model Physiology-based and shows how multiple scales interact to result in system-level response. Active force arises as an internal force out of physiology, unlike prior models which introduced it ad-hoc. Provides a framework to test mechanisms of hearing damage and recovery.
Measurement of vibration signal at the inner hair cell AN https://hms.harvard.edu/news/splitting-hair-cells Challenges: Surgery itself could affect hearing sensitivity (so it needs to be minimized) Optical interferometry method Signal to noise
Guinea pig How are the experiments done? mouse Animal is anaesthetized. Surgery is done to expose the cochlea for experiments. Hearing sensitivity of the animal is constantly assessed during surgery and experimentation. At the end of the experiment, the animal is sacrificed. chinchilla
Classical Method of interferometry needed reflective objects Reflective beads are placed on the organ of Corti for two purposes Enhance the signal to noise Compared to a mirror organ of Corti tissue reflectance <5x10-5 (At the limit of most commercial velocimeters) Localize the exact measurement place Net vibration signal is the integration all signal from along the optical axis of a laser beam.
Apex: Best frequency <500 Hz Reissner s membrane in the way but less vulnerable to mechanical damage Tectorial membrane and apical surface of the hair cells can be seen Basilar membrane cannot be seen (but can be seen with OCT) Apical vs. Basal measurements Apex Base Base: Best Frequency >10 khz Vulnerable to mechanical (surgical) damage Basilar membrane can be seen but the tectorial membrane and the hair cells cannot be seen
Inner ear vibration across tissue organ of Corti in the inner ear Simultaneous measurement of the inner ear structures will help understand hearing loss. Image courtesy of http://www.neuroreille.com/ A technique which can measure the vibration through tissue is needed. And, without opening the bone (cochlear or otic capsule)
Phase-sensitive Fourier domain optical coherence tomography The PSFDOCT system is characterized by: o Michelson Interferometer o Low coherence optical source o Detector array / spectrometer Schematic of a PSFDOCT system The combined light from reference and sample arms are split by a diffraction grating, and component light frequencies, i.e. wavelengths, are detected by a linear detector array. Sample vibration is detected as the path length difference between the reference and sample arms -- through changes in the phase of the Fourier transformed data. Image Courtesy of http://research.vuse.vanderbilt.edu/skalalab/
PSFDOCT set-up cochlea
PSFDOCT measurement in a live guinea pig (Base) We showed that the frequency-tuning varies within a cross-section Reflectance Image Frequency response Schematic Ramamoorthy et al, 2014
Mouse Apex Gao et al (2014) showed fine tuning and amplification in mouse apex using OCT. However, mouse apex has high best-frequencies > 5 khz. May not represent cochlear-processing of human speech.
Range of audibility of the human ear
Guinea pig apex : optical access Guinea pig apex has best-frequencies around 100-1000 Hz, well-representing human speech. But, its apex is not easily accessible. Guinea pig skull To access the guinea pig apex in the axial direction, extensive surgery of the jaw and neck tissue is needed
Optical access in the apex Guinea pig skull Optical access Bulla-edge We introduced a method whereby a miniature mirror is placed inside the bulla to deflect the light by 90 degrees. That reduces the surgery drastically and improves hearing sensitivity during measurements Combining with PSFDOCT, we introduced a very less-invasive method in live guinea pig cochlea to measure apex vibrations (speech processing area).
Pattern of vibrations in guinea pig apex Structural Image Vibration Pattern at 200 Hz nm schematic Higher order vibration-modes at high frequencies
Vibration experiments in vivo: Summary Developed custom-made OCT research instrument to study inner ear vibrations Showed frequency-tuning differences within a crosssection in the basal-region New data in the apex shows complex vibration patterns and base-apex differences Sets the stage for many more studies such as otoacoustic emissions and hearing damage.
Ongoing Auditory Research in our group at IITB At IIT Bombay we do not conduct cochlear physiology experiments in animals Development of methods and sensors to address challenges in in vivo cochlear physiology experiments Simulation of EAS cochlear implants and normal vs. impaired hearing using the MEA model (Ramamoorthy et al., 2007) Interested in improving speech processors by understanding how cochlea processes sound.
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