Dennis Zelle

Extraction of otoacoustic distortion product sources using pulse basis functions

Distortion product otoacoustic emissions (DPOAEs) acquired in normal-hearing subjects show considerable variation in amplitude with varying frequency. This is known as DPOAE fine structure. It is widely accepted that fine structure results from wave interference from two DPOAE sources, a non-linear generation component and a coherent reflection component. Here a method is presented that decomposes short-pulse DPOAE recordings into pulse basis functions and enables the quantification of both source components in the time domain, independent of their relative phase and at low cost of measurement time. Input-output functions utilizing the extracted primary-source component are analyzed.

Level dependence of the nonlinear-distortion component of distortion-product otoacoustic emissions in humans.

Distortion-product otoacoustic emissions (DPOAEs) emerge when presenting two primary tones with different frequencies f1 and f2 to the cochlea and are commonly used in diagnosis and research to evaluate the functional state of the cochlea. Optimal primary-tone stimulus levels accounting for the different level dependencies of the traveling-wave amplitudes of the two primary tones near the f2-tonotopic place on the basilar membrane are often used to maximize DPOAE amplitudes. However, parameters defining the optimal levels can be affected by wave interference between the nonlinear-distortion and coherent-reflection components of the DPOAE. Here, the components were separated in the time domain using a pulsed stimulus paradigm and optimal levels determined. Based on the amplitude dependence of the nonlinear-distortion components on primary-tone stimulus levels, level parameters yielding maximum DPOAE amplitudes were derived for six normal-hearing adults and compared to data recorded with continuous two-tone stimulation. The level parameters resulting from analysis of the nonlinear-distortion components show dependence on stimulus frequency and small standard deviations. DPOAE input/output functions derived for optimal levels exhibit larger slopes, wider dynamic range and less variability across subjects than those derived for conventional stimulus and analysis conditions, potentially increasing their reliability and sensitivity for assessing cochlea function.

Ipsilateral medial olivocochlear reflex adaptation of the primary-source DPOAE component measured with pulsed tones

Measurement of contralateral suppression or ipsilateral adaptation of DPOAE due to the medial olivocochlear reflex (MOCR) in humans has so far been complicated by interference between the two major contributors to a DPOAE signal, namely, the nonlinear and the reflection-source components. For instance, while the MOCR has been shown to act inhibitory to the cochlear amplifier, a considerable share of the measured responses has been reported to be of the excitatory type (e.g. 22% for contralateral adaptation in [11]), and it has been shown that the magnitudes of ipsilateral adaptation as well as contralateral suppression depend on the precise frequency choice relative to the position of dips in the DPOAE fine structure [3, 8]. To separate MOCR effects on both source components, we developed a paradigm consisting of five short f2 pulses presented during a 0.35 s on-period of the f1 primary within blocks of 1.35 s length. The responses at f1 and f2 were cancelled using the primary-tone phase variation techniq...

Latencies of extracted distortion-product otoacoustic source components

Distortion product otoacoustic emissions (DPOAEs) evolve as a byproduct of the nonlinear amplification process of two stimulus tones f2 ≥ f1 in the cochlea. According to a prevailing model, DPOAEs comprise a nonlinear-generation and a coherent-reflection component. Recently, we introduced a new technique using short f2 pulses which enables the extraction of both source components in the time domain by nonlinear least-square curve fitting to decompose the DPOAE response into pulse basis functions (PBFs). The analysis of the extracted DPOAE source components in the time domain enables determination of their latencies which may be used to estimate cochlear frequency tuning. Short-pulse DPOAEs were acquired from 16 subjects for f2 = 1.5, 2, 3, and 4 kHz using six primary-tone levels with L2 = 25 − 65 dB SPL. For the extracted nonlinear-generation and coherent-reflection components, latencies decrease with increasing stimulus frequency and level. The obtained latency values are in accordance with the expected ...

Input-output functions of the nonlinear-distortion component of distortion-product otoacoustic emissions in normal and hearing-impaired human earsa)

Distortion-product otoacoustic emissions (DPOAEs) arise in the cochlea in response to two tones with frequencies f1 and f2 and mainly consist of two components, a nonlinear-distortion and a coherent-reflection component. Wave interference between these components limits the accuracy of DPOAEs when evaluating the function of the cochlea with conventional continuous stimulus tones. Here, DPOAE components are separated in the time domain from DPOAE signals elicited with short stimulus pulses. The extracted nonlinear-distortion components are used to derive estimated distortion-product thresholds (EDPTs) from semi-logarithmic input-output (I/O) functions for 20 normal-hearing and 21 hearing-impaired subjects. I/O functions were measured with frequency-specific stimulus levels at eight frequencies f2 = 1,…, 8 kHz (f2/f1 = 1.2). For comparison, DPOAEs were also elicited with continuous primary tones. Both acquisition paradigms yielded EDPTs, which significantly correlated with behavioral thresholds (p < 0.001) and enabled derivation of estimated hearing thresholds (EHTs) from EDPTs using a linear regression relationship. DPOAE-component separation in the time domain significantly reduced the standard deviation of EHTs compared to that derived from continuous DPOAEs (p < 0.01). In conclusion, using frequency-specific stimulus levels and DPOAE-component separation increases the reliability of DPOAE I/O functions for assessing cochlear function and estimating behavioral thresholds.

Effects of temporal primary-tone arrangement on DPOAE properties in humans

Distortion-product otoacoustic emissions (DPOAEs) emerge as a by-product of the nonlinear amplification of sound waves in the cochlea when presenting two tones of frequencies f1 and f2. According to a widely accepted model, DPOAEs comprise two main components, which can be separated in the time domain using short stimulus pulses. The present study utilized two acquisition paradigms with different primary-tone arrangements, denoted as SP-f1 and SP-f2, to investigate the nonlinear-distortion component arising near the f2-tonotopic site on the basilar membrane. In SP-f2, a conventional paradigm, the f1 tone was presented for 25 ms, whereas the f2 tone was switched on 5 ms after f1 onset for frequency-dependent durations between 3 and 11 ms to elicit the DPOAE. SP-f1 interchanged the temporal arrangement and durations of the primary tones. DPOAEs were recorded at eight frequencies (f2 = 1 – 8 kHz; f2/f1 = 1.2) and five primary-tone levels L2 = 30 – 70 dB SPL in 56 normal-hearing ears from 33 subjects. Compari...

Reduced sound-evoked and resting-state BOLD fMRI connectivity in tinnitus

The exact neurophysiological basis of chronic tinnitus, which affects 10-15% of the population, remains unknown and is controversial at many levels. It is an open question whether phantom sound perception results from increased central neural gain or not, a crucial question for any future therapeutic intervention strategies for tinnitus. We performed a comprehensive study of mild hearing-impaired participants with and without tinnitus, excluding participants with co-occurrences of hyperacusis. A right-hemisphere correlation between tinnitus loudness and auditory perceptual difficulty was observed in the tinnitus group, independent of differences in hearing thresholds. This correlation was linked to reduced and delayed sound-induced suprathreshold auditory brain responses (ABR wave V) in the tinnitus group, suggesting subsided rather than exaggerated central neural responsiveness. When anatomically predefined auditory regions of interest were analysed for altered sound-evoked BOLD fMRI activity, it became evident that subcortical and cortical auditory regions and regions involved in sound detection (posterior insula, hippocampus), responded with reduced BOLD activity in the tinnitus group, emphasizing reduced, rather than increased, central neural gain. Regarding previous findings of evoked BOLD activity being linked to positive connectivities at rest, we additionally analysed r-fcMRI responses in anatomically predefined auditory regions and regions associated with sound detection. A profound reduction in positive interhemispheric connections of homologous auditory brain regions and a decline in the positive connectivities between lower auditory brainstem regions and regions involved in sound detection (hippocampus, posterior insula) were observed in the tinnitus group. The finding went hand-in-hand with the emotional (amygdala, anterior insula) and temporofrontal/stress-regulating regions (prefrontal cortex, inferior frontal gyrus) that were no longer positively connected with auditory cortex regions in the tinnitus group but were instead positively connected to lower-level auditory brainstem regions. Delayed sound processing, reduced sound-evoked BOLD fMRI activity and altered r-fcMRI in the auditory midbrain correlated in the tinnitus group and showed right hemisphere dominance as did tinnitus loudness and perceptual difficulty. The findings suggest that reduced central neural gain in the auditory stream may lead to phantom perception through a failure to energize attentional/stress-regulating networks for contextualization of auditory-specific information. Reduced auditory-specific information flow in tinnitus has until now escaped detection in humans, as low-level auditory brain regions were previously omitted from neuroimaging studies. TRIAL REGISTRATION German Clinical Trials Register DRKS0006332.

GC-B Deficient Mice With Axon Bifurcation Loss Exhibit Compromised Auditory Processing

Sensory axon T-like branching (bifurcation) in neurons from dorsal root ganglia and cranial sensory ganglia depends on the molecular signaling cascade involving the secreted factor C-type natriuretic peptide, the natriuretic peptide receptor guanylyl cyclase B (GC-B; also known as Npr2) and cGMP-dependent protein kinase I (cGKI, also known as PKGI). The bifurcation of cranial nerves is suggested to be important for information processing by second-order neurons in the hindbrain or spinal cord. Indeed, mice with a spontaneous GC-B loss of function mutation (Npr2cn/cn) display an impaired bifurcation of auditory nerve (AN) fibers. However, these mice did not show any obvious sign of impaired basal hearing. Here, we demonstrate that mice with a targeted inactivation of the GC-B gene (Npr2lacZ/lacZ, GC-B KO mice) show an elevation of audiometric thresholds. In the inner ear, the cochlear hair cells in GC-B KO mice were nevertheless similar to those from wild type mice, justified by the typical expression of functionally relevant marker proteins. However, efferent cholinergic feedback to inner and outer hair cells was reduced in GC-B KO mice, linked to very likely reduced rapid efferent feedback. Sound-evoked AN responses of GC-B KO mice were elevated, a feature that is known to occur when the efferent axo-dendritic feedback on AN is compromised. Furthermore, late sound-evoked brainstem responses were significantly delayed in GC-B KO mice. This delay in sound response was accompanied by a weaker sensitivity of the auditory steady state response to amplitude-modulated sound stimuli. Finally, the acoustic startle response (ASR) – one of the fastest auditory responses – and the prepulse inhibition of the ASR indicated significant changes in temporal precision of auditory processing. These findings suggest that GC-B-controlled axon bifurcation of spiral ganglion neurons is important for proper activation of second-order neurons in the hindbrain and is a prerequisite for proper temporal auditory processing likely by establishing accurate efferent top-down control circuits. These data hypothesize that the bifurcation pattern of cranial nerves is important to shape spatial and temporal information processing for sensory feedback control.

Comparison of time-domain source-separation techniques for short-pulse distortion-product otoacoustic emissions

Distortion-product otoacoustic emissions (DPOAEs) are presumed to consist mainly of two components, a nonlinear-distortion component and a coherent-reflection component. Wave interference between these two components reduces the accuracy of DPOAEs when used to evaluate cochlear function. Here, short tone pulses are utilized to record DPOAE signals in normal-hearing subjects. DPOAE components are extracted from recordings at discrete frequencies using two different techniques in the time domain. The extracted DPOAE components are compared to recordings obtained with conventional, continuous primary tones.

Time-domain analysis of distortion-product otoacoustic emissions using a hydrodynamic cochlea model

Abstract As a by-product of nonlinear amplification in the cochlea, the inner ear emits sound waves in response to two tones with different frequencies. These sound waves are measurable in the ear canal as distortion-product otoacoustic emissions (DPOAEs). DPOAEs putatively consist of two components emerging at different locations in the cochlea. Wave interference between the two components limits the accuracy of DPOAEs as a noninvasive measure of cochlear function. Using short stimulus pulses instead of continuous stimuli, the two DPOAE components can be separated in the time domain due to their different latencies. The present work utilizes a nonlinear hydrodynamic cochlea model to simulate short-pulse DPOAEs in the time domain. When adding irregularities to the mechanical parameters of the model, the simulated DPOAE signals show two distinguishable components and long-lasting beat tones, similar to band-pass filtered experimental data from normal-hearing human subjects. The model results suggest that the beat tones can occur solely due to interference of the coherent-reflection component with the fading nonlinear-distortion component.