Predicting lateralization performance at high frequencies from auditory-nerve spike timing

Thesis (M. Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.Includes bibliographical references (leaves 77-82).Psychophysical sensitivity to interaural time differences (ITD) in the envelope of high- frequency sinusoidally amplitude-modulated (SAM) tones is generally poorer than that to low- frequency pure tones (PT). ITD sensitivity at high frequencies might be improved using "transposed stimuli" (TS), which seek to produce the same temporal discharge patters in high- frequency neurons as in low-frequency neurons for PT. Here, we study ITD sensitivity for PT, SAM tones and TS using neurophysiology, psychoacoustics and computational models. Phase locking of auditory-nerve fibers in anesthetized cats was characterized using both the synchronization index and autocorrelograms. With both measures, phase locking is stronger for PT than TS, and for TS than for SAM tones. Phase locking to SAM tones and TS degrades with increasing stimulus level, while remaining more stable for PT. ITD discrimination was measured in humans for stimuli presented either in quiet or with band-reject noise intended to restrict listening to a narrow frequency band. Performance improves slightly with increasing stimulus level for all three stimuli both with and without noise. ITD sensitivity to TS is comparable to PT performance only in the absence of noise. To relate psychophysical performance to auditory-nerve activity, we developed a physiologically-based optimal binaural processor model with delay lines and coincidence detectors. In the no-noise condition, model performance is stable with stimulus level, consistent with psychophysics. However, in the band- reject noise condition, model performance for SAM tones and TS degrades with increasing level. .(cont.) These results have implications for the relative roles of peripheral patterns of activity and the binaural processor in accounting for ITD sensitivity at low versus high frequenciesby Anna Alexandra Dreyer.M.Eng

Coincidence detection in the cochlear nucleus : implications for the coding of pitch

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 165-177).The spatio-temporal pattern in the auditory nerve (AN), i.e. the temporal pattern of AN fiber activity across the tonotopic axis, provides cues to important features in sounds such as pitch, loudness, and spatial location. These spatio-temporal cues may be extracted by central neurons in the cochlear nucleus (CN) that receive inputs from AN fibers innervating different cochlear regions and are sensitive to their relative timing. One possible mechanism for this extraction is cross-frequency coincidence detection (CD), in which a central neuron converts the degree of cross-frequency coincidence in the AN into a rate response by preferentially firing when its AN inputs across the tonotopic axis discharge in synchrony. We implemented a CD model receiving AN inputs from varying extents of the tonotopic axis, and compared responses of model CD cells with those of single units recorded in the CN of the anesthetized cat. We used Huffman stimuli, which have flat magnitude spectra and a single phase transition, to systematically manipulate the relative timing across AN fibers and to evaluate the sensitivity of model CD cells and CN units to the spatiotemporal pattern of AN discharges. Using a maximum likelihood approach, we found that certain unit types (primary-like-with-notch and some phase lockers) had responses consistent with cross-frequency CD cell. Some of these CN units provide input to neurons in a binaural circuit that process cues for sound localization and are sensitive to interaural level differences. A possible functional role of a cross-frequency CD mechanism in the CN is to increase the dynamic range of these binaural neurons. However, many other CN units had responses more consistent with AN fibers than with CD cells. We hypothesized that CN units resembling cross-frequency CD cells (as determined by their responses to Huffman stimuli) would convert spatio-temporal cues to pitch in the AN into rate cues that are robust with level. We found that, in response to harmonic complex tones, cross-frequency CD cells and some CN units (primary-like-with-notch and choppers) maintained robust rate cues at high levels compared to AN fibers, suggesting that at least some CN neurons extend the dynamic range of rate representations of pitch beyond that found in AN fibers. However, there was no obvious correlation between robust rate cues in individual CN units and similarity to cross-frequency CD cells as determined by responses to Huffman stimuli. It is likely that a model including more realistic inputs, membrane channels, and spiking mechanism, or other mechanisms such as lateral inhibition or spatial and temporal summation over spatially distributed inputs would provide insight into the neural mechanisms that give rise to the robust rate cues observed in some CN units.by Grace I. Wang.Ph.D

Electro-anatomical models of the cochlear implant

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2007.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (p. 211-225).While cochlear implantation has become the standard care in treating patients with severe to profound sensorineural hearing loss, the variation in benefit (communicative ability) individual patients derive from implantation remains both large and, for the most part, unexplained. One explanation for this variation is the status of the implanted ear which, when examined histopathologically, also displays substantial variation due to both the pathogenesis of hearing loss (etiology, etc.) and pathological changes initiated by implantation. For instance, across-patient variation in electrode position and insertion depth is clearly present, as are differential amounts of residual spiral ganglion survival, fibrous tissue formation and electrode encapsulation, cochlear ossification, and idiosyncratic damage to adjacent cochlear structures. Because of the complex geometric electrical properties of the tissues found in the implanted ear, demonstrating the impact of pathological variability on neuronal excitation, and ultimately on behavioral performance, will likely require a detailed representation of the peripheral anatomy. Our approach has been to develop detailed, three-dimensional (3D) electro-anatomical models (EAMs) of the implanted ear capable of representing the aforementioned patient-specific types of pathological variation. In response to electric stimulation, these computational models predict an estimate of (1) the 3D electric field, (2) the cochleotopic pattern of neural activation, and (3) the electrically-evoked compound action potential (ECAP) recorded from intracochlear electrodes. This thesis focuses on three aims. First, two patient-specific EAMs are formulated from hundreds of digital images of the histologically-sectioned temporal bones of two patients, attempting to incorporate the detailed pathology of each. Second, model predictions are compared to relevant reports from the literature, data collected from a cohort of implanted research subjects, and, most importantly, to archival data collected during life from the same two patients used to derive our psychophysical threshold measures, and ECAP recordings) collectively show a promising correspondence between model-predicted and empirically-measured data. Third, by making incremental adjustments to the anatomical representation in the model, the impact of individual attributes are investigated, mechanisms that may degrade benefit suggested, and potential interventions explored.by Darren M. Whiten.Ph.D

The Role of the Stereociliary Glycocalyx in Hair Bundle Cohesion

The sensory hair cells of the inner ear are exquisitely sensitive machines that translate the broad dynamic range of sound intensities in our auditory landscape into the electrical language of neurons. The mechanosensitive organelle of the hair cell is the hair bundle, a cluster of linked, finger-like, membrane-ensheathed projections, stereocilia, emerging from the cellʼs apical surface. As a structure, the hair bundle is highly conserved, changing little yet performing many functions throughout the vertebrate evolutionary tree. The mechanosensitivity of the hair bundle is achieved by the tension-gating of mechanosensitive channels joined to proteinaceous tip links that connect the distal tips of neighboring stereocilia along the axis of mechanosensitivity. When the hair bundle is deflected and the distal tips of stereocilia shear in relation to one another, tension is applied to the tip links causing the mechanotransduction channels to open. This allows cations to flow in and depolarize the cell membrane triggering synaptic release at the base of the cell, and consequently sending the information to the brain. The cell membranes in the hair bundle face a difficult task when the bundle oscillates in response to sound. For efficient auditory mechanotransduction, it is essential that all stereocilia move nearly in unison, shearing at their distal tips yet maintaining contact without membrane fusion, yet the mechanism producing this cohesion is unknown nor have physical forces associated with it ever been measured. The mechanism I have tested in my doctoral work is that of counterion-mediated tethering of negatively charged sugars on opposing stereociliary membranes. Using capillary electrophoresis, I demonstrated that the stereociliary glycocalyx acts as a negatively charged polymer brush, necessary for the soundness of the glyco-tethering hypothesis. I found by force-fiber photomicrometry that when the distal tips of stereocilia were brought together they formed elastic attachments in a manner dependent on the presence of N-linked sugars and the surrounding ionic environment. Ca2+- and Mg2+-mediated attachments varied in their strength and susceptibility to overcharging, though Mg2+ played a larger role in the observed adhesion. Both partial deglycosylation and removal of divalent ions from surrounding solutions dramatically reduced adhesiveness. During the process of adhesion between the distal tips of stereocilia, chaotic stick-slip friction was observed and appeared qualitatively similar to stick-slip associated with earthquakes. Together, these results indicate that stereocilia are likely to form glycan- and divalent ionmediated attachments to one another that may provide the necessary cohesion for auditory hair bundles. This indicates the importance of the glycocalyx for hearing, and more generally, the biomechanics of cellular adhesion

Sensory Communication

Contains table of contents for Section 2, an introduction and reports on twelve research projects.National Institutes of Health Grant R01 DC00117National Institutes of Health Grant R01 DC02032National Institutes of Health/National Institute of Deafness and Other Communication Disorders Grant 2 R01 DC00126National Institutes of Health Grant 2 R01 DC00270National Institutes of Health Contract N01 DC-5-2107National Institutes of Health Grant 2 R01 DC00100U.S. Navy - Office of Naval Research Grant N61339-96-K-0002U.S. Navy - Office of Naval Research Grant N61339-96-K-0003U.S. Navy - Office of Naval Research Grant N00014-97-1-0635U.S. Navy - Office of Naval Research Grant N00014-97-1-0655U.S. Navy - Office of Naval Research Subcontract 40167U.S. Navy - Office of Naval Research Grant N00014-96-1-0379U.S. Air Force - Office of Scientific Research Grant F49620-96-1-0202National Institutes of Health Grant RO1 NS33778Massachusetts General Hospital, Center for Innovative Minimally Invasive Therapy Research Fellowship Gran

Centering in parallel channel systems

Several types of signal processing systems in which the signal flows along parallel channels in a fashion similar to the auditory system have been investigated. The effect of excitation with signals containing both single and multiple spectral peaks (formants) was considered. In particular, the effect of nonlinear interaction between channels, referred to as centering, in the presence of noise was studied. These systems were investigated for their value, both as information processing networks and as models of the auditory system. The analysis indicates that parallel channel systems, in general, exhibit excellent performance in the presence of noise, and that a parallel channel system, with a limited overall bandwidth, can be made to process large amounts of information per unit time if used in conjunction with an appropriate centering network. Furthermore, these systems permit detailed frequency analysis of signals in the presence of noise without impairing their temporal discrimination capability. Of the centering processes investigated, maximum likelihood centering provides an optimum estimate of formant frequency in the presence of noise, while lateral inhibitory centering probably represents the most practical process for implementation. The performances of various centering processes are compared to the known characteristics of the auditory system, and the most promising of these, lateral inhibitory centering, is employed in a model of the peripheral auditory system. The response of this model, when simulated on the digital computer, correlates closely with many of the characteristics of the peripheral auditory system. The model, however, does not adequately explain the spectral resolving ability displayed by the ear. An extension of the model was suggested which should not be subject to this limitation

Neural correlates and mechanisms of sounds localization in everyday reverberant settings

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2009.Cataloged from PDF version of thesis.Includes bibliographical references (p. 161-176).Nearly all listening environments-indoors and outdoors alike-are full of boundary surfaces (e.g., walls, trees, and rocks) that produce acoustic reflections. These reflections interfere with the direct sound arriving at a listener's ears, distorting the binaural cues for sound localization. Yet, human listeners have little difficulty localizing sounds in most settings. This thesis addresses fundamental questions regarding the neural basis of sound localization in everyday reverberant environments. In the first set of experiments, we investigate the effects of reverberation on the directional sensitivity of low-frequency auditory neurons sensitive to interaural time differences (ITD), the principal cue for localizing sound containing low frequency energy. Because reverberant energy builds up over time, the source location is represented relatively faithfully during the early portion of a sound, but this representation becomes increasingly degraded later in the stimulus. We show that the directional sensitivity of ITD-sensitive neurons in the auditory midbrain of anesthetized cats and awake rabbits follows a similar time course. However, the tendency of neurons to fire preferentially at the onset of a stimulus results in more robust directional sensitivity than expected, suggesting a simple mechanism for improving directional sensitivity in reverberation. To probe the role of temporal response dynamics, we use a conditioning paradigm to systematically alter temporal response patterns of single neurons. Results suggest that making temporal response patterns less onset-dominated typically leads to poorer directional sensitivity in reverberation. In parallel behavioral experiments, we show that human lateralization judgments are consistent with predictions from a population rate model for decoding the observed midbrain responses, suggesting a subcortical origin for robust sound localization in reverberant environments. In the second part of the thesis we examine the effects of reverberation on directional sensitivity of neurons across the tonotopic axis in the awake rabbit auditory midbrain. We find that reverberation degrades the directional sensitivity of single neurons, although the amount of degradation depends on the characteristic frequency and the type of binaural cues available. When ITD is the only available directional cue, low frequency neurons sensitive to ITD in the fine-time structure maintain better directional sensitivity in reverberation than high frequency neurons sensitive to ITD in the envelope. On the other hand, when both ITD and interaural level differences (ILD) cues are available, directional sensitivity is comparable throughout the tonotopic axis, suggesting that, at high frequencies, ILDs provide better directional information than envelope ITDs in reverberation. These findings can account for results from human psychophysical studies of spatial hearing in reverberant environments. This thesis marks fundamental progress towards elucidating the neural basis for spatial hearing in everyday settings. Overall, our results suggest that the information contained in the rate responses of neurons in the auditory midbrain is sufficient to account for human sound localization in reverberant environments.by Sasha Devore.Ph.D

Precision and reliability of cochlear nerve response in mice lacking functional synaptic ribbons

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2009.Cataloged from PDF version of thesis.Includes bibliographical references (p. 87-99).Synaptic ribbons are electron-dense structures surrounded by vesicles and anchored to the presynaptic membrane of photoreceptors, retinal bipolar cells and hair cells. Ribbon synapses are characterized by sustained exocytosis that is graded with stimulus intensity and can achieve high release rates. Leading hypotheses implicate the ribbon in maintenance of a large readily releasable pool (RRP) of presynaptic vesicles which enables rapid and precisely-timed exocytosis that supports instantaneous discharge rates of well over 1000 spikes per second. To gain insight into the function of this specialized presynaptic molecular machinery, we characterized the response properties of single auditory nerve (AN) fibers in a mouse with targeted deletion of a presynaptic scaffolding gene, bassoon, in which ribbons are no longer anchored to the active zone. Since each mammalian AN fiber usually receives input from a single inner hair cell active zone to which a single ribbon is typically anchored, single-fiber recordings from bassoon mutants and control mice offer a sensitive functional metric of the contribution of individual ribbons to neural function. Response properties of mutant AN fibers were similar, in many respects, to wild-type. Spike intervals remained irregular, thresholds were unaffected, dynamic range was unchanged, spike synchronization to(cont.) stimulus phase was unimpaired, the time course of post-onset adaptation and recovery from adaptation were normal, and the ability to sustain discharge throughout a long-duration stimulus was unaffected. These data indicate that the presynaptic mechanisms which regulate precise timing of exocytosis, graded release rates and sustained neurotransmitter release were not impaired by loss of the ribbon. However, reductions were seen in spontaneous and sound-evoked AN fiber discharge rates, coinciding with an increased variance of first spike timing to stimulus onset. Unlike fibers from wild-type mice, mutants failed to show increased peak rate as stimulus onset became more abrupt. The reduction of peak rates and increased first spike variance likely result from degraded reliability of discharge to stimulus onset via a mechanism such as reduced RRP size. Thus, the ribbon appears to support a large RRP that enables the rapid onset rates necessary for the auditory system to resolve stimulus features key for many perceptual tasks.by Bradley N. Buran.Ph.D