Sripriya Ramamoorthy

A mechano-electro-acoustical model for the cochlea: Response to acoustic stimuli

A linear, physiologically based, three-dimensional finite element model of the cochlea is developed. The model integrates the electrical, acoustic, and mechanical elements of the cochlea. In particular, the model includes interactions between structures in the organ of Corti (OoC), piezoelectric relations for outer hair cell (OHC) motility, hair bundle (HB) conductance that changes with HB deflection, current flow in the cross section and along the different scalae, and the feed-forward effect. The parameters in the model are based on guinea-pig data as far as possible. The model is vetted using a variety of experimental data on basilar membrane motion and data on voltages and currents in the OoC. Model predictions compare well, qualitatively and quantitatively, with experimental data on basilar membrane frequency response, impulse response, frequency glides, and scala tympani voltage. The close match of the model predictions with experimental data demonstrates the validity of the model for simulating cochlear response to acoustic input and for testing hypotheses of cochlear function. Analysis of the model and its results indicates that OHC somatic motility is capable of powering active amplification in the cochlea. At the same time, the model supports a possible synergistic role for HB motility in cochlear amplification.

In vivo outer hair cell length changes expose the active process in the cochlea

Background Mammalian hearing is refined by amplification of the sound-evoked vibration of the cochlear partition. This amplification is at least partly due to forces produced by protein motors residing in the cylindrical body of the outer hair cell. To transmit power to the cochlear partition, it is required that the outer hair cells dynamically change their length, in addition to generating force. These length changes, which have not previously been measured in vivo, must be correctly timed with the acoustic stimulus to produce amplification. Methodology/Principal Findings Using in vivo optical coherence tomography, we demonstrate that outer hair cells in living guinea pigs have length changes with unexpected timing and magnitudes that depend on the stimulus level in the sensitive cochlea. Conclusions/Significance The level-dependent length change is a necessary condition for directly validating that power is expended by the active process presumed to underlie normal hearing.

Filtering of Acoustic Signals within the Hearing Organ

The detection of sound by the mammalian hearing organ involves a complex mechanical interplay among different cell types. The inner hair cells, which are the primary sensory receptors, are stimulated by the structural vibrations of the entire organ of Corti. The outer hair cells are thought to modulate these sound-evoked vibrations to enhance hearing sensitivity and frequency resolution, but it remains unclear whether other structures also contribute to frequency tuning. In the current study, sound-evoked vibrations were measured at the stereociliary side of inner and outer hair cells and their surrounding supporting cells, using optical coherence tomography interferometry in living anesthetized guinea pigs. Our measurements demonstrate the presence of multiple vibration modes as well as significant differences in frequency tuning and response phase among different cell types. In particular, the frequency tuning at the inner hair cells differs from other cell types, causing the locus of maximum inner hair cell activation to be shifted toward the apex of the cochlea compared with the outer hair cells. These observations show that additional processing and filtering of acoustic signals occur within the organ of Corti before inner hair cell excitation, representing a departure from established theories.

Minimal basilar membrane motion in low-frequency hearing

Significance To perceive speech, the brain relies on inputs from sensory cells located near the top of the spiral-shaped cochlea. This low-frequency region of the inner ear is anatomically difficult to access, and it has not previously been possible to study its mechanical response to sound in intact preparations. Here, we used optical coherence tomography to image sound-evoked vibration inside the intact cochlea. We show that low-frequency sound moves a small portion of the basilar membrane, and that the motion declines in an exponential manner across the basilar membrane. Hence, the response of the hearing organ to speech-frequency sounds is different from the one evident in high-frequency cochlear regions. Low-frequency hearing is critically important for speech and music perception, but no mechanical measurements have previously been available from inner ears with intact low-frequency parts. These regions of the cochlea may function in ways different from the extensively studied high-frequency regions, where the sensory outer hair cells produce force that greatly increases the sound-evoked vibrations of the basilar membrane. We used laser interferometry in vitro and optical coherence tomography in vivo to study the low-frequency part of the guinea pig cochlea, and found that sound stimulation caused motion of a minimal portion of the basilar membrane. Outside the region of peak movement, an exponential decline in motion amplitude occurred across the basilar membrane. The moving region had different dependence on stimulus frequency than the vibrations measured near the mechanosensitive stereocilia. This behavior differs substantially from the behavior found in the extensively studied high-frequency regions of the cochlea.

A theoretical study of structural acoustic silencers for hydraulic systems

Theoretical studies show that the introduction of an in-line structural acoustic silencer into a hydraulic system can achieve broadband quieting (i.e., high transmission loss). Strategies for using structural acoustic filters for simultaneously reducing reflection and transmission by tailoring the material properties are studied. A structural acoustic silencer consists of a flexible layer inserted into nominally rigid hydraulic piping. Transmission loss is achieved by two mechanisms--reflection of energy due to an impedance mismatch, and coupling of the incoming acoustic fluctuations to structural vibrations thereby allowing for the extraction of energy through losses in the structure. Structural acoustic finite element simulations are used to determine the transmission loss and evaluate designs. Results based on the interaction of orthotropic and isotropic plates with variable geometry, operating in heavy fluids like water and oil, are presented.

Persistence of Past Stimulations: Storing Sounds within the Inner Ear

Tones cause vibrations within the hearing organ. Conventionally, these vibrations are thought to reflect the input and therefore end with the stimulus. However, previous recordings of otoacoustic emissions and cochlear microphonic potentials suggest that the organ of Corti does continue to move after the end of a tone. These after-vibrations are characterized here through recordings of basilar membrane motion and hair cell extracellular receptor potentials in living anesthetized guinea pigs. We show that after-vibrations depend on the level and frequency of the stimulus, as well as on the sensitivity of the ear. Even a minor loss of hearing sensitivity caused a sharp reduction in after-vibration amplitude and duration. Mathematical models suggest that after-vibrations are driven by energy added into organ of Corti motion after the end of an acoustic stimulus. The possible importance of after-vibrations for psychophysical phenomena such as forward masking and gap detection are discussed.

The Biophysical Origin of Traveling-Wave Dispersion in the Cochlea

Sound processing begins at the peripheral auditory system, where it undergoes a highly complex transformation and spatial separation of the frequency components inside the cochlea. This sensory signal processing constitutes a neurophysiological basis for psychoacoustics. Wave propagation in the cochlea, as shown by measurements of basilar membrane velocity and auditory nerve responses to sound, has demonstrated significant frequency modulation (dispersion), in addition to tonotopic gain and active amplification. The physiological and physical basis for this dispersion remains elusive. In this article, a simple analytical model is presented, along with experimental validation using physiological measurements from guinea pigs, to identify the origin of traveling-wave dispersion in the cochlea. We show that dispersion throughout the cochlea is fundamentally due to the coupled fluid-structure interaction between the basilar membrane and the scala fluids. It is further influenced by the variation in physical and geometrical properties of the basilar membrane, the sensitivity or gain of the hearing organ, and the relative dominance of the compression mode at about one-third octave beyond the best frequency.

Structural acoustic silencers—Design and experiment

The effectiveness of introducing flexible structural layers into air conveying ducts for controlling noise is investigated through theoretical and experimental means, focusing at low frequencies where conventional passive silencing technology is least effective. Previous theoretical work has shown that using flexible rather than rigid walls has the potential to achieve high transmission losses. The physical mechanisms responsible for structural acoustic silencing, including the relation between transmission loss peaks and structural resonance corresponding to different transverse structural modes, are presented. Sensitivity of the performance to acoustic and structural boundary conditions is discussed. To eliminate radiated noise from these walls (breakout noise), a rigid walled cavity is introduced under the flexible plate. The challenge is to find means to reject plane waves in the two-duct system. Designs that overcome these issues and achieve appreciable transmission loss are investigated. Results based on three-dimensional finite element simulations are compared with experimental results.

Minimally invasive surgical method to detect sound processing in the cochlear apex by optical coherence tomography

Abstract. Sound processing in the inner ear involves separation of the constituent frequencies along the length of the cochlea. Frequencies relevant to human speech (100 to 500 Hz) are processed in the apex region. Among mammals, the guinea pig cochlear apex processes similar frequencies and is thus relevant for the study of speech processing in the cochlea. However, the requirement for extensive surgery has challenged the optical accessibility of this area to investigate cochlear processing of signals without significant intrusion. A simple method is developed to provide optical access to the guinea pig cochlear apex in two directions with minimal surgery. Furthermore, all prior vibration measurements in the guinea pig apex involved opening an observation hole in the otic capsule, which has been questioned on the basis of the resulting changes to cochlear hydrodynamics. Here, this limitation is overcome by measuring the vibrations through the unopened otic capsule using phase-sensitive Fourier domain optical coherence tomography. The optically and surgically advanced method described here lays the foundation to perform minimally invasive investigation of speech-related signal processing in the cochlea.

Thin and open vessel windows for intra-vital fluorescence imaging of murine cochlear blood flow

Normal microvessel structure and function in the cochlea is essential for maintaining the ionic and metabolic homeostasis required for hearing function. Abnormal cochlear microcirculation has long been considered an etiologic factor in hearing disorders. A better understanding of cochlear blood flow (CoBF) will enable more effective amelioration of hearing disorders that result from aberrant blood flow. However, establishing the direct relationship between CoBF and other cellular events in the lateral wall and response to physio-pathological stress remains a challenge due to the lack of feasible interrogation methods and difficulty in accessing the inner ear. Here we report on new methods for studying the CoBF in a mouse model using a thin or open vessel-window in combination with fluorescence intra-vital microscopy (IVM). An open vessel-window enables investigation of vascular cell biology and blood flow permeability, including pericyte (PC) contractility, bone marrow cell migration, and endothelial barrier leakage, in wild type and fluorescent protein-labeled transgenic mouse models with high spatial and temporal resolution. Alternatively, the thin vessel-window method minimizes disruption of the homeostatic balance in the lateral wall and enables study CoBF under relatively intact physiological conditions. A thin vessel-window method can also be used for time-based studies of physiological and pathological processes. Although the small size of the mouse cochlea makes surgery difficult, the methods are sufficiently developed for studying the structural and functional changes in CoBF under normal and pathological conditions.