Human tectorial membrane waves

Thesis (Ph. D.)--Massachusetts Institute of Technology, Department of Electrical Engineering and Computer Science, 2013.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references (pages 107-114).by Shirin Farrahi.Ph.D

In-vivo measurement of sound-induced motions in the gerbil cochlea

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2010.Cataloged from PDF version of thesis.Includes bibliographical references (p. 53-54).We developed methods to measure sound-induced motions in a live mammalian cochlea using a laser Doppler velocimeter (LDV). We measured the basilar membrane (BM) in the Mongolian gerbil at a distance of roughly 1.5 mm from the extreme base and found a best frequency (BF) of roughly 35 kHz. We chose the base to gain access through the round window membrane (RWM) to minimize the need for invasive surgery. Post-mortem measurements showed a 20dB drop in sensitivity as well as a half-octave drop in BF. The post-mortem phase led the in vivo phase below the BF and lagged the in vivo phase above the BF. These features of the post-mortem response agree with those seen by Overstreet [10] in the base of the gerbil cochlea. To look for evidence of radial modes in the BM, we measured points along the radius of the BM both in vivo and post-mortem. In the in vivo case, we found slightly sharper tuning in the center of the BM than on the edge but similar phase excursions. In the post-mortem case, we found similar bandwidths and phase excursions along the radius of the BM. Since in vivo measurements along the radius of the BM were only collected in one animal, we cannot yet conclude that there are multiple radial modes in the gerbil BM. In addition, our in vivo preparation was relatively insensitive as evidenced by compound action potential (CAP) thresholds greater than 80dB SPL in the region of interest.(cont.) We identified the removal of the RWM as the cause for elevated CAP thresholds by comparing the CAP thresholds before and after removing the RWM to drop beads on the BM as essential reflective targets. Previous studies also suggest that large CAP threshold increases are common in the gerbil base ([10], [6]). Similar techniques have led to greater success in larger mammals; however, we hope to apply the lessons learned from measuring the in vivo gerbil cochlea to mice, the only species that would allow us to determine the micromechanical changes underlying genetic hearing disorders.by Shirin Farrahi.S.M

Porosity Controls Spread of Excitation in Tectorial Membrane Traveling Waves

Cochlear frequency selectivity plays a key role in our ability to understand speech, and is widely believed to be associated with cochlear amplification. However, genetic studies targeting the tectorial membrane (TM) have demonstrated both sharper and broader tuning with no obvious changes in hair bundle or somatic motility mechanisms. For example, cochlear tuning of Tectb[superscript –/–] mice is significantly sharper than that of Tecta[superscript Y1870C/+] mice, even though TM stiffnesses are similarly reduced relative to wild-type TMs. Here we show that differences in TM viscosity can account for these differences in tuning. In the basal cochlear turn, nanoscale pores of Tecta[superscript Y1870C/+] TMs are significantly larger than those of Tectb[superscript –/–] TMs. The larger pore size reduces shear viscosity (by ∼70%), thereby reducing traveling wave speed and increasing spread of excitation. These results demonstrate the previously unrecognized importance of TM porosity in cochlear and neural tuning.National Institutes of Health (U.S.) (Grant R01-DC00238)National Science Foundation (U.S.). Graduate Research Fellowship Program (Grant 1122374)National Institutes of Health (U.S.) (Training Grant

Micro Fuel Cell Testbench

The Micro Fuel Cell Testbench is a product in development that is intended for use in the laboratory environment for rigorous testing of novel direct methanol fuel cells (DMFCs). Additionally, the MFC Testbench will be able to operate as a stand-alone unit during tradeshows. The main testing operations of the device will include monitoring the operating voltage and current of the DMFC in response to variable load. The unit will also monitor the ambient temperature and humidity while the fuel cell is operating

Longitudinal spread of mechanical excitation through tectorial membrane traveling waves

The mammalian inner ear separates sounds by their frequency content, and this separation underlies important properties of human hearing, including our ability to understand speech in noisy environments. Studies of genetic disorders of hearing have demonstrated a link between frequency selectivity and wave properties of the tectorial membrane (TM). To understand these wave properties better, we developed chemical manipulations that systematically and reversibly alter TM stiffness and viscosity. Using microfabricated shear probes, we show that (i) reducing pH reduces TM stiffness with little change in TM viscosity and (ii) adding PEG increases TM viscosity with little change in TM stiffness. By applying these manipulations in measurements of TM waves, we show that TM wave speed is determined primarily by stiffness at low frequencies and by viscosity at high frequencies. Both TM viscosity and stiffness affect the longitudinal spread of mechanical excitation through the TM over a broad range of frequencies. Increasing TM viscosity or decreasing stiffness reduces longitudinal spread of mechanical excitation, thereby coupling a smaller range of best frequencies and sharpening tuning. In contrast, increasing viscous loss or decreasing stiffness would tend to broaden tuning in resonance-based TM models. Thus, TM wave and resonance mechanisms are fundamentally different in the way they control frequency selectivity.National Institutes of Health (U.S.) (Grant R01-DC000238)National Science Foundation (U.S.). Graduate Research Fellowship (Grant 1122374)National Institutes of Health (U.S.) (Training Grant

Tectorial membrane porosity controls spread of excitation and tuning in the cochlea

Modifications of genes that encode proteins found exclusively in the tectorial membrane (TM) alter mechanical properties and produce a wide range of hearing deficits. However, the changes in TM physical properties responsible for these deficits remain unclear. In particular, the cochlear tuning of Tectb[superscript −/−] mice is significantly sharper than that of Tecta[superscript Y1870C/+] mice, even though the stiffnesses of Tecta[superscript Y1870C/+] and Tectb[superscript −/−] TMs are similarly reduced relative to wild-type TMs. Here we show that differences in TM wave properties that are governed by shear viscosity account for these differences in tuning. The shear viscosity of the TM results from the interaction of interstitial fluid with the porous structure of the TM’s macromolecular matrix. In basal regions of the cochlea, nanoscale pores of Tecta[superscript Y1870C/+] TMs are significantly larger than those of Tectb[superscript −/−] TMs. The larger pores in Tecta[superscript Y1870C/+] TMs gives rise to lower shear viscosity (by ∼70%), which in turn, reduces wave speed and increases wave decay constants relative to Tectb[superscript −/−] TM wave properties. These results demonstrate the importance of TM porosity in cochlear tuning and that TM porosity, not stiffness, underlies the striking differences in hearing between Tecta[superscript Y1870C/+] and Tectb[superscript −/−] mice.National Institutes of Health (U.S.) (Grant R01-DC00238)National Science Foundation (U.S.) (Grant 1122374

Electrokinetic properties of the mammalian tectorial membrane

The tectorial membrane (TM) clearly plays a mechanical role in stimulating cochlear sensory receptors, but the presence of fixed charge in TM constituents suggests that electromechanical properties also may be important. Here, we measure the fixed charge density of the TM and show that this density of fixed charge is sufficient to affect mechanical properties and to generate electrokinetic motions. In particular, alternating currents applied to the middle and marginal zones of isolated TM segments evoke motions at audio frequencies (1–1,000 Hz). Electrically evoked motions are nanometer scaled (~5–900 nm), decrease with increasing stimulus frequency, and scale linearly over a broad range of electric field amplitudes (0.05–20 kV/m). These findings show that the mammalian TM is highly charged and suggest the importance of a unique TM electrokinetic mechanism.National Institutes of Health (U.S.) (Grant R01-DC0023)National Institutes of Health (U.S.). (Harvard University--MIT Speech and Hearing Bioscience and Technology Program Training Grant

Subjective Expectations in the Context of HIV/AIDS in Malawi

In this paper we present a newly-developed interactive elicitation methodology to collect probabilistic expectations in a developing country context with low levels of literacy and numeracy, and we evaluate the feasibility and success of this method for a wide range of outcomes in rural Malawi. We find that respondent’s answers about subjective expectations respect basic properties of probabilities, and vary meaningfully with observable characteristics and past experience. From a substantive point of view, the elicited expectations indicate that individuals are generally aware of differential risks. For example, individuals with less income and less land feel rightly at more risk of financial distress than people with higher SES, or people who are divorced or widow feel rightly at more risk of being infected with HIV than currently married individuals. While many expectations—including also the probability of being currently infected with HIV—are well-calibrated compared to actual probabilities, mortality expectations are substantially over-estimated compared to lifetable estimates. This overestimation may lead individuals to underestimate the benefits of adopting HIV risk-reduction strategies. The skewed distribution of expectations about condom use also suggests that a small group of innovators are the forerunners in the adoption of condoms within marriage for HIV prevention

Picoliter Wells from Selective Growth of HEK293 Cells on Chemically Modified PDMS Surfaces

In this study, a method for the rapid generation of a variety of bifunctional surfaces that can serve to quickly determine the selective adhesion of HEK293 cells towards different chemical functionalities has been established. Using the information about selective adhesion of HEK293 cells to bifunctional surfaces, we demonstrate the ability to construct stable, high density, and multi-welled surfaces where the mammalian cells form the walls of picoliter volume wells.NRC publication: Ye

Tectorial Membrane Traveling Waves Underlie Sharp Auditory Tuning in Humans

Our ability to understand speech requires neural tuning with high frequency resolution, but the peripheral mechanisms underlying sharp tuning in humans remain unclear. Sharp tuning in genetically modified mice has been attributed to decreases in spread of excitation of tectorial membrane traveling waves. Here we show that the spread of excitation of tectorial membrane waves is similar in humans and mice, although the mechanical excitation spans fewer frequencies in humans—suggesting a possible mechanism for sharper tuning.National Institutes of Health (U.S.) (Grant R01-DC00238