A Model-Based Approach for Separating the Cochlear Microphonic from the Auditory Nerve Neurophonic in the Ongoing Response Using Electrocochleography

Electrocochleography (ECochG) is a potential clinically valuable technique for predicting speech perception outcomes in cochlear implant (CI) recipients, among other uses. Current analysis is limited by an inability to quantify hair cell and neural contributions which are mixed in the ongoing part of the response to low frequency tones. Here, we used a model based on source properties to account for recorded waveform shapes and to separate the combined signal into its components. The model for the cochlear microphonic (CM) was a sinusoid with parameters for independent saturation of the peaks and the troughs of the responses. The model for the auditory nerve neurophonic (ANN) was the convolution of a unit potential and population cycle histogram with a parameter for spread of excitation. Phases of the ANN and CM were additional parameters. The average cycle from the ongoing response was the input, and adaptive fitting identified CM and ANN parameters that best reproduced the waveform shape. Test datasets were responses recorded from the round windows of CI recipients, from the round window of gerbils before and after application of neurotoxins, and with simulated signals where each parameter could be manipulated in isolation. Waveforms recorded from 284 CI recipients had a variety of morphologies that the model fit with an average r2 of 0.97 ± 0.058 (standard deviation). With simulated signals, small systematic differences between outputs and inputs were seen with some variable combinations, but in general there were limited interactions among the parameters. In gerbils, the CM reported was relatively unaffected by the neurotoxins. In contrast, the ANN was strongly reduced and the reduction was limited to frequencies of 1,000 Hz and lower, consistent with the range of strong neural phase-locking. Across human CI subjects, the ANN contribution was variable, ranging from nearly none to larger than the CM. Development of this model could provide a means to isolate hair cell and neural activity that are mixed in the ongoing response to low-frequency tones. This tool can help characterize the residual physiology across CI subjects, and can be useful in other clinical settings where a description of the cochlear physiology is desirable

Tuning to Interaural Time Differences across Frequency

Interaural time differences (ITDs) are an important cue for azimuthal sound localization. Sensitivity to this cue depends on temporal synchrony to the waveform (i.e., phase locking) that begins in the hair cells and is relayed to the neural comparators. The synchrony function is low-pass. Therefore, it is expected that neural tuning to ITDs will become narrower with frequency according to a 1/frequency function. To test this, we measured ITD tuning across frequency in neurons from the superior olivary complex, the dorsal nucleus of the lateral lemniscus, the inferior colliculus, the auditory thalamus, and the auditory cortex. For some neurons in each nucleus, the ITD tuning width did become systematically narrower by the expected 1/frequency relationship. However, in other neurons the ITD tuning width was nearly constant across frequency. Constant ITD tuning width was infrequently observed in neurons of the superior olivary complex but was common in neurons in structures above the superior olivary complex. The nearly constant ITD tuning was caused both by sharper ITD tuning at low frequencies and broader tuning at higher frequencies within the low-frequency band. Neurons with nearly constant tuning to ITDs may be the mechanism underlying the perception of ITDs in humans in which just-noticeable differences to changes in ITD decrease by less than the 1/frequency prediction

The TLC: A Novel Auditory Nucleus of the Mammalian Brain

[EN]We have identified a novel nucleus of the mammalian brain and termed it the tectal longitudinal column (TLC). Basic histologic stains, tract-tracing techniques and three-dimensional reconstructions reveal that the rat TLC is a narrow, elongated structure spanning themidbrain tectum longitudinally. This paired nucleus is located close to the midline, immediately dorsal to the periaqueductal gray matter.It occupies what has traditionally been considered the most medial region of the deep superior colliculus and the most medial region of the inferior colliculus. The TLC differs from the neighboring nuclei of the superior and inferior colliculi and the periaqueductal gray by its distinct connections and cytoarchitecture. Extracellular electrophysiological recordings show that TLC neurons respond to auditory stimuli with physiologic properties that differ from those of neurons in the inferior or superior colliculi. We have identified the TLC in rodents, lagomorphs, carnivores, nonhuman primates, and humans, which indicates that the nucleus is conserved across mammals. The discovery of the TLC reveals an unexpected level of longitudinal organization in the mammalian tectum and raises questions as to the participation of this mesencephalic region in essential, yet completely unexplored, aspects of multisensory and/or sensorimotorintegration.[ES]Hemos identificado un nuevo núcleo del cerebro de los mamíferos y lo hemos denominado columna longitudinal tectal (CLT; TLC por sus siglas en inglés). Mediante tinciones histológicas básicas, técnicas de trazado de vías nerviosas y reconstrucciones tridimensionales hemos observado que la CLT es una estructura larga y estrecha que recorre longitudinalmente el techo mesencefálico. Este núcleo par se encuentra próximo a la línea media, inmediatamente dorsal con respecto a la sustancia gris periacueductal. Ocupa un territorio considerado tradicionalmente como la región más medial de las capas profundas del colículo superior y la región más medial del colículo inferior. La CLT difiere de los núcleos que la rodean (colícuo superior, colículo inferior y sustancia gris periacueductal) por sus conexiones y su citoarquitectura. Los registros electrofisiológicos extracelulares muestran que las neuronas de la CLT responden a los estímulos auditivos y que sus propiedades de respuesta son distintas de las de las neuronas de los colículos superior e inferior. Hemos identificado la TLC en el cerebro de roedores, lagomorfos, carnívoros, primates no humanos y seres humanos, lo que indica que el núcleo está filogenéticamente conservado en una gran variedad de mamíferos. El descubrimiento de la CLT revela un insospechado nivel de organización longitudinal en el techo mesencefálico de los mamíferos y suscita preguntas sobre la participación de esta región mesencefálica en aspectos esenciales de la integración multisensorial y/o sensorimotora que hasta ahora no han sido estudiados

The organization of frequency and binaural cues in the gerbil inferior colliculus: GRAÑA et al.

The inferior colliculus (IC) is the common target of separate pathways that transmit different types of auditory information. Beyond tonotopy, little is known about the organization of response properties within the 3-dimensional layout of the auditory midbrain in most species. Through study of interaural time difference (ITD) processing, the functional properties of neurons can be readily characterized and related to specific pathways. To characterize the representation of ITDs relative to the frequency and hodological organization of the IC, the properties of neurons were recorded and the sites recovered histologically. Subdivisions of the IC were identified based on cytochrome oxidase (CO) histochemistry. The results were plotted within a framework formed by an MRI atlas of the gerbil brain. The central nucleus was composed of two parts, and lateral and dorsal cortical areas were identified. The lateral part of the central nucleus had the highest CO activity in the IC and a high proportion of neurons sensitive to ITDs. The medial portion had lower CO activity and fewer ITD-sensitive neurons. A common tonotopy with a dorsolateral to ventromedial gradient of low to high frequencies spanned the two regions. The distribution of physiological responses was in close agreement with known patterns of ascending inputs. An understanding of the 3-dimensional organization of the IC is needed to specify how the single tonotopic representation in the IC central nucleus leads to the multiple tonotopic representations in core areas of the auditory cortex

Intraoperative electrocochleographic characteristics of auditory neuropathy spectrum disorder in cochlear implant subjects

Auditory neuropathy spectrum disorder (ANSD) is characterized by an apparent discrepancy between measures of cochlear and neural function based on auditory brainstem response (ABR) testing. Clinical indicators of ANSD are a present cochlear microphonic (CM) with small or absent wave V. Many identified ANSD patients have speech impairment severe enough that cochlear implantation (CI) is indicated. To better understand the cochleae identified with ANSD that lead to a CI, we performed intraoperative round window electrocochleography (ECochG) to tone bursts in children (n = 167) and adults (n = 163). Magnitudes of the responses to tones of different frequencies were summed to measure the “total response” (ECochG-TR), a metric often dominated by hair cell activity, and auditory nerve activity was estimated visually from the compound action potential (CAP) and auditory nerve neurophonic (ANN) as a ranked “Nerve Score”. Subjects identified as ANSD (45 ears in children, 3 in adults) had higher values of ECochG-TR than adult and pediatric subjects also receiving CIs not identified as ANSD. However, nerve scores of the ANSD group were similar to the other cohorts, although dominated by the ANN to low frequencies more than in the non-ANSD groups. To high frequencies, the common morphology of ANSD cases was a large CM and summating potential, and small or absent CAP. Common morphologies in other groups were either only a CM, or a combination of CM and CAP. These results indicate that responses to high frequencies, derived primarily from hair cells, are the main source of the CM used to evaluate ANSD in the clinical setting. However, the clinical tests do not capture the wide range of neural activity seen to low frequency sounds

Assessment of cochlear synaptopathy by electrocochleography to low frequencies in a preclinical model and human subjects

Cochlear synaptopathy is the loss of synapses between the inner hair cells and the auditory nerve despite survival of sensory hair cells. The findings of extensive cochlear synaptopathy in animals after moderate noise exposures challenged the long-held view that hair cells are the cochlear elements most sensitive to insults that lead to hearing loss. However, cochlear synaptopathy has been difficult to identify in humans. We applied novel algorithms to determine hair cell and neural contributions to electrocochleographic (ECochG) recordings from the round window of animal and human subjects. Gerbils with normal hearing provided training and test sets for a deep learning algorithm to detect the presence of neural responses to low frequency sounds, and an analytic model was used to quantify the proportion of neural and hair cell contributions to the ECochG response. The capacity to detect cochlear synaptopathy was validated in normal hearing and noise-exposed animals by using neurotoxins to reduce or eliminate the neural contributions. When the analytical methods were applied to human surgical subjects with access to the round window, the neural contribution resembled the partial cochlear synaptopathy present after neurotoxin application in animals. This result demonstrates the presence of viable hair cells not connected to auditory nerve fibers in human subjects with substantial hearing loss and indicates that efforts to regenerate nerve fibers may find a ready cochlear substrate for innervation and resumption of function

Interaural Time Discrimination of Envelopes Carried on High-Frequency Tones as a Function of Level and Interaural Carrier Mismatch

The present study investigated interaural time discrimination for binaurally mismatched carrier frequencies in listeners with normal hearing. One goal of the investigation was to gain insights into binaural hearing in patients with bilateral cochlear implants, where the coding of interaural time differences may be limited by mismatches in the neural populations receiving stimulation on each side

Correlation of Early Auditory Potentials and Intracochlear Electrode Insertion Properties: An Animal Model Featuring Near Real-Time Monitoring

The goal of this work was to assess electrophysiologic response changes to acoustic stimuli as an intracochlear electrode impacted cochlear structures in an animal model of hearing preservation cochlear implantation. The ultimate goal is to develop efficient procedures for assessing the status of cochlear physiology for intraoperative use

The Compound Action Potential in Subjects Receiving a Cochlear Implant

The compound action potential (CAP) is a purely neural component of the cochlea’s response to sound, and may provide information about the existing neural substrate in cochlear implant (CI) subjects that can help account for variance in speech perception outcomes

Flexible cochlear microendoscopy in the gerbil

To validate the scientific utility of flexible cochlear microendoscopy in the gerbil. This model is currently being developed to study the effects of intracochlear electrode positioning on functional parameters