Compound Action Potential Of Auditory Nerve Research Articles

Effects of contralateral noise on envelope-following responses, auditory-nerve compound action potentials, and otoacoustic emissions measured simultaneously.

This study assessed whether the effects of contralateral acoustic stimulation (CAS) are consistent with eliciting the medial olivocochlear (MOC) reflex for measurements sensitive to outer hair cell (otoacoustic emissions, OAEs), auditory-nerve (AN; compound action potential, CAP), and brainstem/cortical (envelope-following response, EFR) function. The effects of CAS were evaluated for simultaneous measurement of OAEs, CAPs, and EFRs in participants with normal hearing. Clicks were presented at 40 or 98 Hz in three ipsilateral noise conditions (no noise, 45 dB SPL, and 55 dB SPL). For the no noise condition, CAS suppressed or enhanced EFR amplitudes for 40- and 98-Hz clicks, respectively, while CAS had no significant effect on CAP amplitudes. A follow-up experiment using slower rates (4.4-22.2 Hz) assessed whether this insignificant CAS effect on CAPs was from ipsilateral MOC stimulation or AN adaptation; however, CAS effects remained insignificant despite favorable signal-to-noise ratios. CAS-related enhancements of EFR and CAP amplitudes in ipsilateral noise were not observed, contrary to the anti-masking effect of the MOC reflex. EFR and OAE suppression from CAS were not significantly correlated. Thus, the effects of CAS on EFRs may not be solely mediated by the MOC reflex and may be partially mediated by higher auditory centers.

A Guinea Pig Model Suggests That Objective Assessment of Acoustic Hearing Preservation in Human Ears With Cochlear Implants Is Confounded by Shifts in the Spatial Origin of Acoustically Evoked Potential Measurements Along the Cochlear Length.

Our recent empirical findings have shown that the auditory nerve compound action potential (CAP) evoked by a low-level tone burst originates from a narrow cochlear region tuned to the tone burst frequency. At moderate to high sound levels, the origins shift to the most sensitive audiometric regions rather than the extended high-frequency regions of the cochlear base. This means that measurements evoked from extended high-frequency sound stimuli can shift toward the apex with increasing level. Here we translate this study to understand the spatial origin of acoustically evoked responses from ears that receive cochlear implants, an emerging area of research and clinical practice that is not completely understood. An essential step is to first understand the influence of the cochlear implant in otherwise naive ears. Our objective was to understand how function of the high-frequency cochlear base, which can be excited by the intense low-frequency sounds that are frequently used for objective intra- and postoperative monitoring, can be influenced by the presence of the cochlear implant. We acoustically evoked responses and made measurements with an electrode placed near the guinea pig round window. The cochlear implant was not utilized for either electrical stimulation or recording purposes. With the cochlear implant in situ, CAPs were acoustically evoked from 2 to 16 kHz tone bursts of various levels while utilizing the slow perfusion of a kainic acid solution from the cochlear apex to the cochlear aqueduct in the base, which sequentially reduced neural responses from finely spaced cochlear frequency regions. This cochlear perfusion technique reveals the spatial origin of evoked potential measurements and provides insight on what influence the presence of an implant has on acoustical hearing. Threshold measurements at 3 to 11 kHz were elevated by implantation. In an individual ear, thresholds were elevated and lowered as cochlear implant was respectively inserted and removed, indicative of "conductive hearing loss" induced by the implant. The maximum threshold elevation occurred at most sensitive region of the naive guinea pig ear (33.66 dB at 8 kHz), making 11 kHz the most sensitive region to acoustic sounds for guinea pig ears with cochlear implants. Conversely, the acute implantation did not affect the low-frequency, 500 Hz thresholds and suprathreshold function, as shown by the auditory nerve overlapped waveform. As the sound pressure level of the tone bursts increased, mean data show that the spatial origin of CAPs along the cochlear length shifted toward the most sensitive cochlear region of implanted ears, not the extended high-frequency cochlear regions. However, data from individual ears showed that after implantation, measurements from moderate to high sound pressure levels originate in places that are unique to each ear. Alterations to function of the cochlear base from the in situ cochlear implant may influence objective measurements of implanted ears that are frequently made with intense low-frequency sound stimuli. Our results from guinea pigs advance the interpretation of measurements used to understand how and when residual acoustic hearing is lost in human ears receiving a cochlear implant.

Evidence That Ultrafast Nonquantal Transmission Underlies Synchronized Vestibular Action Potential Generation.

Amniotes evolved a unique postsynaptic terminal in the inner ear vestibular organs called the calyx that receives both quantal and nonquantal (NQ) synaptic inputs from Type I sensory hair cells. The nonquantal synaptic current includes an ultrafast component that has been hypothesized to underlie the exceptionally high synchronization index (vector strength) of vestibular afferent neurons in response to sound and vibration. Here, we present three lines of evidence supporting the hypothesis that nonquantal transmission is responsible for synchronized vestibular action potentials of short latency in the guinea pig utricle of either sex. First, synchronized vestibular nerve responses are unchanged after administration of the AMPA receptor antagonist CNQX, while auditory nerve responses are completely abolished. Second, stimulus evoked vestibular nerve compound action potentials (vCAP) are shown to occur without measurable synaptic delay and three times shorter than the latency of auditory nerve compound action potentials (cCAP), relative to the generation of extracellular receptor potentials. Third, paired-pulse stimuli designed to deplete the readily releasable pool (RRP) of synaptic vesicles in hair cells reveal forward masking in guinea pig auditory cCAPs, but a complete lack of forward masking in vestibular vCAPs. Results support the conclusion that the fast component of nonquantal transmission at calyceal synapses is indefatigable and responsible for ultrafast responses of vestibular organs evoked by transient stimuli.SIGNIFICANCE STATEMENT The mammalian vestibular system drives some of the fastest reflex pathways in the nervous system, ensuring stable gaze and postural control for locomotion on land. To achieve this, terrestrial amniotes evolved a large, unique calyx afferent terminal which completely envelopes one or more presynaptic vestibular hair cells, which transmits mechanosensory signals mediated by quantal and nonquantal (NQ) synaptic transmission. We present several lines of evidence in the guinea pig which reveals the most sensitive vestibular afferents are remarkably fast, much faster than their auditory nerve counterparts. Here, we present neurophysiological and pharmacological evidence that demonstrates this vestibular speed advantage arises from ultrafast NQ electrical synaptic transmission from Type I hair cells to their calyx partners.

Computational modeling of the human compound action potential.

The auditory nerve (AN) compound action potential (CAP) is an important tool for assessing auditory disorders and monitoring the health of the auditory periphery during surgical procedures. The CAP has been mathematically conceptualized as the convolution of a unit response (UR) waveform with the firing rate of a population of AN fibers. Here, an approach for predicting experimentally recorded CAPs in humans is proposed, which involves the use of human-based computational models to simulate AN activity. CAPs elicited by clicks, chirps, and amplitude-modulated carriers were simulated and compared with empirically recorded CAPs from human subjects. In addition, narrowband CAPs derived from noise-masked clicks and tone bursts were simulated. Many morphological, temporal, and spectral aspects of human CAPs were captured by the simulations for all stimuli tested. These findings support the use of model simulations of the human CAP to refine existing human-based models of the auditory periphery, aid in the design and analysis of auditory experiments, and predict the effects of hearing loss, synaptopathy, and other auditory disorders on the human CAP.

Minimum Detectable Differences in Electrocochleography Measurements: Bayesian-Based Predictions.

Physiology of the cochlea and auditory nerve can be assessed with electrocochleography (ECochG), a technique that involves measuring auditory evoked potentials from an electrode placed near or within the cochlea. Research, clinical, and operating room applications of ECochG have in part centered on measuring the auditory nerve compound action potential (AP) amplitude, the summating potential (SP) amplitude, and the ratio of the two (SP/AP). Despite the common use of ECochG, the variability of repeated amplitude measurements for individuals and groups is not well understood. We analyzed ECochG measurements made with a tympanic membrane electrode in a group of younger normal-hearing participants to characterize the within-participant and group-level variability for the AP amplitude, SP amplitude, and SP/AP amplitude ratio. Results show that the measurements have substantial variability and that, especially with smaller sample sizes, significant reduction in variability can be obtained by averaging measurements across repeated electrode placements within subjects. Using a Bayesian-based model of the data, we generated simulated data to predict minimum detectable differences in AP and SP amplitudes for experiments with a given number of participants and repeated measurements. Our findings provide evidence-based recommendations for the design and sample size determination of future experiments using ECochG amplitude measurements, and the evaluation of previous publications in terms of sensitivity to detecting experimental effects on ECochG amplitude measurements. Accounting for the variability of ECochG measurements should result in more consistent results in the clinical and basic assessments of hearing and hearing loss, either hidden or overt.

Electrocochleography in cochlear implantation: Development, applications, and future directions.

Electrocochleography (ECochG) is an electrophysiological technique that records electrical potentials generated by different components of the inner ear and peripheral cochlear nerve in response to acoustic stimulation. ECochG responses can be analyzed into (1) cochlear microphonics (CM), (2) auditory nerve neurophonics, (3) summating potential, and (4) compound action potential. Over the past few decades, there have been ongoing refinements in technique and updates in the understanding of recorded potentials. Historically, ECochG found its main application in the diagnostic evaluation of Meniere's disease (MD). However, in the last decade, the focus has shifted towards cochlear implantation (CI). In patients with residual hearing after CI, combined electric and acoustic stimulation has resulted in improved hearing and speech outcomes. Despite efforts to mitigate trauma during electrode insertion, hearing preservation rates vary after surgery. During implantation, real‐time ECochG offers an opportunity to measure frequency specific CMs elicited from a localized region in the cochlea as the surgeon inserts the electrode array. In extracochlear ECochG recordings, the recording electrode can be placed on the promontory, the stapes, or the tympanic membrane. Intracochlear ECochG can be performed by inserting a recording electrode into the cochlea or by using one of the CI electrodes as the recording electrode. The loss of intraoperative ECochG signal may indicate cochlear trauma from electrode insertion, but the association between intraoperative ECochG changes and cochlear trauma remains controversial. The ability to monitor cochlear trauma during CI electrode placement holds promise to improve hearing preservation outcomes, modify surgical techniques, and change electrode design. The goal of this review is to provide a comprehensive overview of the electrophysiology and history of ECochG, discuss its recent applications in CI, and explore the ongoing research in this expanding field.

Contrasting mechanisms for hidden hearing loss: Synaptopathy vs myelin defects.

Hidden hearing loss (HHL) is an auditory neuropathy characterized by normal hearing thresholds but reduced amplitudes of the sound-evoked auditory nerve compound action potential (CAP). In animal models, HHL can be caused by moderate noise exposure or aging, which induces loss of inner hair cell (IHC) synapses. In contrast, recent evidence has shown that transient loss of cochlear Schwann cells also causes permanent auditory deficits in mice with similarities to HHL. Histological analysis of the cochlea after auditory nerve remyelination showed a permanent disruption of the myelination patterns at the heminode of type I spiral ganglion neuron (SGN) peripheral terminals, suggesting that this defect could be contributing to HHL. To shed light on the mechanisms of different HHL scenarios observed in animals and to test their impact on type I SGN activity, we constructed a reduced biophysical model for a population of SGN peripheral axons whose activity is driven by a well-accepted model of cochlear sound processing. We found that the amplitudes of simulated sound-evoked SGN CAPs are lower and have greater latencies when heminodes are disorganized, i.e. they occur at different distances from the hair cell rather than at the same distance as in the normal cochlea. These results confirm that disruption of heminode positions causes desynchronization of SGN spikes leading to a loss of temporal resolution and reduction of the sound-evoked SGN CAP. Another mechanism resulting in HHL is loss of IHC synapses, i.e., synaptopathy. For comparison, we simulated synaptopathy by removing high threshold IHC-SGN synapses and found that the amplitude of simulated sound-evoked SGN CAPs decreases while latencies remain unchanged, as has been observed in noise exposed animals. Thus, model results illuminate diverse disruptions caused by synaptopathy and demyelination on neural activity in auditory processing that contribute to HHL as observed in animal models and that can contribute to perceptual deficits induced by nerve damage in humans.

The Spatial Origins of Cochlear Amplification Assessed by Stimulus-Frequency Otoacoustic Emissions

Cochlear amplification of basilar membrane traveling waves is thought to occur between a tone’s characteristic frequency (CF) place and within one octave basal of the CF. Evidence for this view comes only from the cochlear base. Stimulus-frequency otoacoustic emissions (SFOAEs) provide a noninvasive alternative to direct measurements of cochlear motion that can be measured across a wide range of CF regions. Coherent reflection theory indicates that SFOAEs arise mostly from the peak region of the traveling wave, but several studies using far-basal suppressor tones claimed that SFOAE components originate many octaves basal of CF. We measured SFOAEs while perfusing guinea pig cochleas from apex to base with salicylate or KCl solutions that reduced outer-hair-cell function and SFOAE amplification. Solution effects on inner hair cells reduced auditory nerve compound action potentials (CAPs) and provided reference times for when solutions reached the SFOAE-frequency CF region. As solution flowed from apex to base, SFOAE reductions generally occurred later than CAP reductions and showed that the effects of cochlear amplification usually peaked ∼1/2 octave basal of the CF region. For tones ≥2 kHz, cochlear amplification typically extended ∼1.5 octaves basal of CF, and the data are consistent with coherent reflection theory. SFOAE amplification did not extend to the basal end of the cochlea, even though reticular lamina motion is amplified in this region, which indicates that reticular lamina motion is not directly coupled to basilar membrane traveling waves. Previous reports of SFOAE-frequency residuals produced by suppressor frequencies far above the SFOAE frequency are most likely due to additional sources created by the suppressor. For some tones <2 kHz, SFOAE amplification extended two octaves apical of CF, which highlights that different vibratory motions produce SFOAEs and CAPs, and that the amplification region depends on the cochlear mode of motion considered. The concept that there is a single “cochlear amplification region” needs to be revised.

Cochlear compound action potentials from high-level tone bursts originate from wide cochlear regions that are offset toward the most sensitive cochlear region.

Little is known about the spatial origins of auditory nerve (AN) compound action potentials (CAPs) evoked by moderate to intense sounds. We studied the spatial origins of AN CAPs evoked by 2- to 16-kHz tone bursts at several sound levels by slowly injecting kainic acid solution into the cochlear apex of anesthetized guinea pigs. As the solution flowed from apex to base, it sequentially reduced CAP responses from low- to high-frequency cochlear regions. The times at which CAPs were reduced, combined with the cochlear location traversed by the solution at that time, showed the cochlear origin of the removed CAP component. For low-level tone bursts, the CAP origin along the cochlea was centered at the characteristic frequency (CF). As sound level increased, the CAP center shifted basally for low-frequency tone bursts but apically for high-frequency tone bursts. The apical shift was surprising because it is opposite the shift expected from AN tuning curve and basilar membrane motion asymmetries. For almost all high-level tone bursts, CAP spatial origins extended over 2 octaves along the cochlea. Surprisingly, CAPs evoked by high-level low-frequency (including 2 kHz) tone bursts showed little CAP contribution from CF regions ≤ 2 kHz. Our results can be mostly explained by spectral splatter from the tone-burst rise times, excitation in AN tuning-curve "tails," and asynchronous AN responses to high-level energy ≤ 2 kHz. This is the first time CAP origins have been identified by a spatially specific technique. Our results show the need for revising the interpretation of the cochlear origins of high-level CAPs-ABR wave 1. NEW & NOTEWORTHY Cochlear compound action potentials (CAPs) and auditory brain stem responses (ABRs) are routinely used in laboratories and clinics. They are typically interpreted as arising from the cochlear region tuned to the stimulus frequency. However, as sound level is increased, the cochlear origins of CAPs from tone bursts of all frequencies become very wide and their centers shift toward the most sensitive cochlear region. The standard interpretation of CAPs and ABRs from moderate to intense stimuli needs revision.

Persistent Auditory Nerve Damage Following Kainic Acid Excitotoxicity in the Budgerigar (Melopsittacus undulatus).

Permanent loss of auditory nerve (AN) fibers occurs with increasing age and sound overexposure, sometimes without hair cell damage or associated audiometric threshold elevation. Rodent studies suggest effects of AN damage on central processing and behavior, but these species have limited capacity to discriminate low-frequency speech-like sounds. Here, we introduce a new animal model of AN damage in an avian communication specialist, the budgerigar (Melopsittacus undulatus). The budgerigar is a vocal learner and speech mimic with sensitive low-frequency hearing and human-like behavioral sensitivity to many complex signals including speech components. Excitotoxic AN damage was induced through bilateral cochlear infusions of kainic acid (KA). Acute KA effects on cochlear function were assessed using AN compound action potentials (CAPs) and hair cell cochlear microphonics (CMs). Long-term KA effects were assessed using auditory brainstem response (ABR) measurements for up to 31weeks post-KA exposure. KA infusion immediately abolished AN CAPs while having mild impact on the CM. ABR wave I, the far-field AN response, showed a pronounced 40-75% amplitude reduction at moderate-to-high sound levels that persisted for the duration of the study. In contrast, wave I latency and the amplitude of wave V were nearly unaffected by KA, and waves II-IV were less reduced than wave I. ABR thresholds, calculated based on complete response waveforms, showed no impairment following KA. These results demonstrate that KA exposure in the budgerigar causes irreversible AN damage, most likely through excitotoxic injury to afferent fibers or synapses as in other species, while sparing ABR thresholds. Normal wave V amplitude, assumed to originate centrally, may persist through compensatory mechanisms that restore central response amplitude by downregulating inhibition. Future studies in this new animal model of AN damage can explore effects of this neural lesion, in isolation from hair cell trauma and threshold elevation, on central processing and perception of complex sounds.

Contralateral Inhibition of Click- and Chirp-Evoked Human Compound Action Potentials.

Cochlear outer hair cells (OHC) receive direct efferent feedback from the caudal auditory brainstem via the medial olivocochlear (MOC) bundle. This circuit provides the neural substrate for the MOC reflex, which inhibits cochlear amplifier gain and is believed to play a role in listening in noise and protection from acoustic overexposure. The human MOC reflex has been studied extensively using otoacoustic emissions (OAE) paradigms; however, these measurements are insensitive to subsequent “downstream” efferent effects on the neural ensembles that mediate hearing. In this experiment, click- and chirp-evoked auditory nerve compound action potential (CAP) amplitudes were measured electrocochleographically from the human eardrum without and with MOC reflex activation elicited by contralateral broadband noise. We hypothesized that the chirp would be a more optimal stimulus for measuring neural MOC effects because it synchronizes excitation along the entire length of the basilar membrane and thus evokes a more robust CAP than a click at low to moderate stimulus levels. Chirps produced larger CAPs than clicks at all stimulus intensities (50–80 dB ppeSPL). MOC reflex inhibition of CAPs was larger for chirps than clicks at low stimulus levels when quantified both in terms of amplitude reduction and effective attenuation. Effective attenuation was larger for chirp- and click-evoked CAPs than for click-evoked OAEs measured from the same subjects. Our results suggest that the chirp is an optimal stimulus for evoking CAPs at low stimulus intensities and for assessing MOC reflex effects on the auditory nerve. Further, our work supports previous findings that MOC reflex effects at the level of the auditory nerve are underestimated by measures of OAE inhibition.

Transient auditory nerve demyelination as a new mechanism for hidden hearing loss

Hidden hearing loss (HHL) is a recently described auditory neuropathy believed to contribute to speech discrimination and intelligibility deficits in people with normal audiological tests. Animals and humans with HHL have normal auditory thresholds but defective cochlear neurotransmission, that is, reduced suprathreshold amplitude of the sound-evoked auditory nerve compound action potential. Currently, the only cellular mechanism known for HHL is loss of inner hair cell synapses (synaptopathy). Here we report that transient loss of cochlear Schwann cells results in permanent auditory deficits characteristic of HHL. This auditory neuropathy is not associated with synaptic loss, but rather with disruption of the first heminodes at the auditory nerve peripheral terminal. Thus, this study identifies a new mechanism for HHL, highlights the long-term consequences of transient Schwann cell loss on hearing and might provide insights into the causes of the auditory deficits reported in patients that recover from acute demyelinating diseases such as Guillain–Barré syndrome.

Electrically Evoked Medial Olivocochlear Efferent Effects on Stimulus Frequency Otoacoustic Emissions in Guinea Pigs.

Stimulus frequency otoacoustic emissions (SFOAEs) are produced by cochlear irregularities reflecting energy from the peak region of the traveling wave (TW). Activation of medial olivocochlear (MOC) efferents reduces cochlear amplification and otoacoustic emissions (OAEs). In other OAEs, MOC activation can produce enhancements. The extent of MOC enhancements of SFOAEs has not been previously studied. In anesthetized guinea pigs, we electrically stimulated MOC fibers and recorded their effects on SFOAEs. MOC stimulation mostly inhibited SFOAEs but sometimes enhanced them. Some enhancements were not near response dips and therefore cannot be explained by a reduction of wavelet cancelations. MOC stimulation always inhibited auditory-nerve compound action potentials showing that cochlear-amplifier gain was not increased. We propose that some SFOAE enhancements arise because shocks excite only a small number of MOC fibers that inhibit a few scattered outer hair cells thereby changing (perhaps increasing) cochlear irregularities and SFOAE amplitudes. Contralateral sound activation is expected to excite approximately one third of MOC efferents and may also change cochlear irregularities. Some papers suggest that large SFOAE components originate far basal of the TW peak, basal of the region that receives cochlear amplification. Using a time-frequency analysis, we separated SFOAEs into components with different latencies. At all SFOAE latencies, most SFOAE components were inhibited by MOC stimulation, but some were enhanced. The MOC inhibition of short-latency SFOAE components is consistent with these components being produced in the cochlear-amplified region near the TW peak.

Treatment with Piribedil and Memantine Reduces Noise-Induced Loss of Inner Hair Cell Synaptic Ribbons.

Noise overstimulation can induce loss of synaptic ribbons associated with loss of Inner Hair Cell – Auditory Nerve synaptic connections. This study examined if systemic administration of Piribedil, a dopamine agonist that reduces the sound evoked auditory nerve compound action potential and/or Memantine, an NMDA receptor open channel blocker, would reduce noise-induced loss of Inner Hair Cell ribbons. Rats received systemic Memantine and/or Piribedil for 3 days before and 3 days after a 3 hour 4 kHz octave band noise at 117 dB (SPL). At 21 days following the noise there was a 26% and 38% loss of synaptic ribbons in regions 5.5 and 6.5 mm from apex, respectively, elevations in 4-, 8- and 20 kHz tonal ABR thresholds and reduced dynamic output at higher intensities of stimulation. Combined treatment with Piribedil and Memantine produced a significant reduction in the noise-induced loss of ribbons in both regions and changes in ABR sensitivity and dynamic responsiveness. Piribedil alone gave significant reduction in only the 5.5 mm region and Memantine alone did not reach significance in either region. Results identify treatments that could prevent the hearing loss and hearing disorders that result from noise-induced loss of Inner Hair Cell – Auditory Nerve synaptic connections.

Central Auditory Processing of Temporal and Spectral-Variance Cues in Cochlear Implant Listeners.

Cochlear implant (CI) listeners have difficulty understanding speech in complex listening environments. This deficit is thought to be largely due to peripheral encoding problems arising from current spread, which results in wide peripheral filters. In normal hearing (NH) listeners, central processing contributes to segregation of speech from competing sounds. We tested the hypothesis that basic central processing abilities are retained in post-lingually deaf CI listeners, but processing is hampered by degraded input from the periphery. In eight CI listeners, we measured auditory nerve compound action potentials to characterize peripheral filters. Then, we measured psychophysical detection thresholds in the presence of multi-electrode maskers placed either inside (peripheral masking) or outside (central masking) the peripheral filter. This was intended to distinguish peripheral from central contributions to signal detection. Introduction of temporal asynchrony between the signal and masker improved signal detection in both peripheral and central masking conditions for all CI listeners. Randomly varying components of the masker created spectral-variance cues, which seemed to benefit only two out of eight CI listeners. Contrastingly, the spectral-variance cues improved signal detection in all five NH listeners who listened to our CI simulation. Together these results indicate that widened peripheral filters significantly hamper central processing of spectral-variance cues but not of temporal cues in post-lingually deaf CI listeners. As indicated by two CI listeners in our study, however, post-lingually deaf CI listeners may retain some central processing abilities similar to NH listeners.

Recording potentials from scala media, saccule and utricle in mice

ObjectiveTo describe a protocol for recording electrical potentials from the scala media, saccule, and utricle in mice. MethodCBA/J mice were used and potentials were recorded with glass electrodes inserted through the basilar membrane using a patch clamp system. ResultsResting potentials were successfully recorded from the scala media, saccule and utricle using described protocols. ConclusionsWith the method described, one can measure resting potentials from the scala media, saccule and utricle, as well as cochlear microphonics (CM) and even auditory nerve compound action potentials (CAP), in a single mouse.

The olivocochlear reflex strength and cochlear sensitivity are independently modulated by auditory cortex microstimulation.

In mammals, efferent projections to the cochlear receptor are constituted by olivocochlear (OC) fibers that originate in the superior olivary complex. Medial and lateral OC neurons make synapses with outer hair cells and with auditory nerve fibers, respectively. In addition to the OC system, there are also descending projections from the auditory cortex that are directed towards the thalamus, inferior colliculus, cochlear nucleus, and superior olivary complex. Olivocochlear function can be assessed by measuring a brainstem reflex mediated by auditory nerve fibers, cochlear nucleus neurons, and OC fibers. Although it is known that the OC reflex is activated by contralateral acoustic stimulation and produces a suppression of cochlear responses, the influence of cortical descending pathways in the OC reflex is largely unknown. Here, we used auditory cortex electrical microstimulation in chinchillas to study a possible cortical modulation of cochlear and auditory nerve responses to tones in the absence and presence of contralateral noise. We found that cortical microstimulation produces two different peripheral modulations: (i) changes in cochlear sensitivity evidenced by amplitude modulation of cochlear microphonics and auditory nerve compound action potentials and (ii) enhancement or suppression of the OC reflex strength as measured by auditory nerve responses, which depended on the intersubject variability of the OC reflex. Moreover, both corticofugal effects were not correlated, suggesting the presence of two functionally different efferent pathways. These results demonstrate that auditory cortex electrical microstimulation independently modulates the OC reflex strength and cochlear sensitivity.

Peripheral effects of the cortico-olivocochlear efferent system

The auditory efferent system comprises descending pathways from the auditory cortex to the cochlea, allowing modulation of sensory processing even at the most peripheral level. Although the presence of descending circuits that connect the cerebral cortex with olivocochlear neurons have been reported in several species, the functional role of the cortico-olivocochlear efferent system remains largely unknown. We have been studying the influence of cortical descending pathways on cochlear responses in chinchillas. Here, we recorded cochlear microphonics and auditory-nerve compound action potentials in response to tones (1–8 kHz; 30–90 dB SPL) before, during, and after auditory-cortex lidocaine or cooling inactivation (n = 20). In addition, we recorded cochlear potentials in the presence and absence of contralateral noise, before, during, and after auditory-cortex micro-stimulation (2-50 μA, 32 Hz rate) (n = 15). Both types of auditory-cortex inactivation produced changes in the amplitude of cochlear potentials. In addition, in the microstimulation experiments, we found an increase of the suppressive effects of contralateral noise in neural responses to 2–4 kHz tones. In conclusion, we demonstrated that auditory-cortex basal activity exerts tonic influences on the olivocochlear system and that auditory-cortex electrical micro-stimulation enhances the suppressive effects of the acoustic evoked olivocochlear reflex. [Work supported by FONDECYT 1120256; FONDECYT 3130635 and Fundacion Puelma.]

Auditory cortex basal activity modulates cochlear responses in chinchillas.

BackgroundThe auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system.Methodology/Principal FindingsCochlear microphonics (CM), auditory-nerve compound action potentials (CAP) and auditory cortex evoked potentials (ACEP) were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments) and a permanent reduction in five chinchillas (lesion experiments). We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses.Conclusions/SignificanceThese results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the obtained effects suggests that there are at least two functional pathways from the auditory cortex to the cochlea.

Electrode configuration influences electrically evoked compound action potentials of guinea pig

The intracochlear electrode array of cochlear implants is used to electrically stimulate the residual hearing auditory nerve of profound sensorineural hearing loss. The present products used to implant possess configuration with the different contact style and different separation between the contacts. This study investigated the effects of electrode configuration on the auditory nerve compound action potentials in response to electric stimulation. We also investigated the channel interaction of the different electrode configuration. Adult guinea pigs were used in acute experimental sessions. We implanted three kinds of electrode array either (1) a narrow spacing banded array consisting of a tapered silicone elastomer carrier with a linear series of banding contacts; or (2) two wider spacing arrays consisting of a tapered silicone elastomer carrier with oval-shaped contacts. The electrically evoked compound action potential (ECAP) was recorded from the intracochlear. ECAP latency functions indicated that the electrode array with narrow spacing and banded contacts generated shorter latency than the electrode array with wider spacing and oval-shaped contacts. We also observed that the electrode array with banded contacts had greater ECAP amplitude than the electrode with oval-shaped contacts.