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Responses of neurons to click-pairs as simulated echoes: auditory nerve to auditory cortex.

When two identical sounds are presented from different locations with a short interval between them, the perception is of a single sound source at the location of the leading sound. This "precedence effect" is an important behavioral phenomenon whose neural basis is being increasingly studied. For this report, neural responses were recorded to paired clicks with varying interstimulus intervals, from several structures of the ascending auditory system in unanesthetized animals. The structures tested were the auditory nerve, anteroventral cochlear nucleus, superior olivary complex, inferior colliculus, and primary auditory cortex. The main finding is a progressive increase in the duration of the suppressive effect of the leading sound (the conditioner) on the response to the lagging sound (the probe). The first major increase occurred between the lower brainstem and inferior colliculus, and the second between the inferior colliculus and auditory cortex. In neurons from the auditory nerve, cochlear nucleus, and superior olivary complex, 50% recovery of the response to the probe occurred, on average, for conditioner and probe intervals of approximately 2 ms. In the inferior colliculus, 50% recovery occurred at an average separation of approximately 7 ms, and in the auditory cortex at approximately 20 ms. Despite these increases in average recovery times, some neurons in every structure showed large responses to the probe within the time window for precedence (approximately 1-4 ms for clicks). This indicates that during the period of the precedence effect, some information about echoes is retained. At the other extreme, for some cortical neurons the conditioner suppressed the probe response for intervals of up to 300 ms. This is in accord with behavioral results that show dominance of the leading sound for an extended period beyond that of the precedence effect. Other transformations as information ascended included an increased variety in the shapes of the recovery functions in structures subsequent to the nerve, and neurons "tuned" to particular conditioner-probe intervals in the auditory cortex. These latter are reminiscent of neurons tuned to echo delay in bats, and may contribute to the perception of the size of the acoustic space.

Acoustic Stimulation↗

Facial nerve stimulation by a cochlear implant in a hemodialysis patient with bone of low mineral density.

Facial nerve stimulation by an activated cochlear implant was noted in a 56-year-old patient who had undergone cochlear implant with a Nucleus 22 implant 2 years previously as treatment for total sensorineural hearing loss following meningitis at age 54. Past history was complicated by total renal failure for which hemodialysis had been required during the past 13 years. Facial spasm occurred 5 months postoperatively with activation of the basal electrodes (channels 13 and 15 of the implant). The facial stimulation was eliminated by deprogramming these electrodes. High-resolusion computed tomography (CT) scanning was unable to demonstrate lucency of the otic capsule and cochlear ossification, but basal electrodes of the implant could be identified near the labyrinthine segment of the facial nerve. To further evaluate bone changes in the patient, the total and regional bone mineral density (BMD) of the head and radius was measured by dual energy X-ray absorptiometry. All BMD values of the patient were markedly low when compared to those of 62 other hemodialysis patient. These findings demonstrate that facial nerve stimulation can occur in the presence of low impedance due to cortical bone changes induced by long-term hemodialysis.

Absorptiometry, Photon↗

Central projections of auditory-nerve fibers of differing spontaneous rate. I. Anteroventral cochlear nucleus.

Auditory nerve fibers have been subdivided into three functional groups (Liberman, M.C. [1978] J. Acoust. Soc. Am. 63:442-455) differing in acoustic sensitivity and spontaneous discharge rate (SR). Using intracellular injection of horseradish peroxidase, the present study analyzes the projections of these three neuronal subclasses to the various subdivisions of the anteroventral cochlear nucleus (AVCN) and to the different cell types found therein. The average number of swellings and number of cells contacted decreased from low- to medium- to high-SR groups. However, these differences in terminal elaboration were not evenly distributed throughout the AVCN. The small cell cap was almost exclusively innervated by low- and medium-SR fibers, i.e., those with the highest acoustic thresholds. Within anterior AVCN, spherical-cell innervation was seen from all SR groups, whereas almost all multipolar cell innervation was from low- and medium-SR fibers. In the posterior AVCN, multipolar-cell innervation was equally likely from all SR groups, whereas globular cells were preferentially contacted by high-SR fibers. These SR-based trends in cochlear nucleus innervation help explain some of the known physiological properties of cell-types in each subdivision. They also suggest that additional physiological study of the small cell cap may be key in elucidating the functional significance of the low-SR population.

Action Potentials↗

Pharmacologic evidence for synaptic transmission mediated by non-N-methyl-D-aspartate receptors in the avian cochlear nucleus.

The hypothesis that synaptic transmission between the auditory nerve and the cochlear nucleus is mediated by an excitatory amino acid acting through N-methyl-D-aspartate (NMDA) receptors was examined in an in vitro preparation of the chicken brainstem. The ability of various bath-applied excitatory amino acid receptor antagonists to inhibit synaptically-evoked responses was assessed by recording field potentials from nucleus magnocellularis (NM) following electrical stimulation of the cochlear nerve. Antagonists that selectively block responses mediated by NMDA receptors, such as D-alpha-aminoadipate and 2-amino-5-phosphonovalerate, were without effect on evoked transmission in NM. In contrast, antagonists that additionally act on non-NMDA receptors, such as cis-2,3-piperidine dicarboxylate and gamma-D-glutamylglycine, reversibly suppressed transmission. The results indicate that (1) transmission in the chicken auditory system is mediated by non-NMDA receptors, and (2) a substance(s) chemically akin to aspartate and glutamate may be the transmitter used by the auditory nerve in NM.

Animals↗

Transneuronal labeling of cochlear nucleus neurons by HRP-labeled auditory nerve fibers and olivocochlear branches in mice.

Auditory nerve fibers were labeled by extracellular injections of horseradish peroxidase into the spiral ganglion in mice. The labeled fibers were traced in an anterograde direction through the auditory nerve into the cochlear nucleus. In almost half of the injections, the labeled endings of auditory nerve fibers contacted cochlear nucleus neurons that were also labeled with horseradish peroxidase and were presumably transneuronally labeled. Only darkly labeled endings were associated with transneuronally labeled neurons, but not all darkly labeled endings had targets that were transneuronally labeled. Transneuronal labeling occurred almost exclusively in the ventral cochlear nucleus, often between endbulbs and bushy cells. Both "modified" endbulbs and the larger endbulbs of Held transneuronally labeled the bushy cells that they contacted. At the ultrastructural level, transneuronal labeling was evident as a darkening of ribosomes and the membrane surfaces of mitochondria, endoplasmic reticulum, and the nucleus. Transneuronal labeling occurred rarely in octopus, small, and stellate cells, and in neurons of the dorsal cochlear nucleus. Spiral ganglion injections also label olivocochlear fibers, efferent fibers that pass through the ganglion en route to the hair cells. These fibers give off branches to the cochlear nucleus that were rarely associated with transneuronal labeling. In eight instances, the targets of olivocochlear branches were stellate cells or small cells. We suggest that in our mouse preparation, horseradish peroxidase is effective as a transneuronal marker because the short distance from injection site to the cochlear nucleus results in a high concentration of horseradish peroxidase in the endings of the auditory nerve fibers.

Afferent Pathways↗

Cochlear pathology following chronic electrical stimulation of the auditory nerve: II. Deafened kittens.

The present study examines the effects of long-term electrical stimulation of the auditory nerve on cochlear histopathology and spiral ganglion cell survival in young sensorineural deafened cats. Eight kittens were deafened using kanamycin and ethacrynic acid, and implanted with bipolar or monopolar scala tympani electrodes. Following recovery from surgery the animals were unilaterally stimulated using charge balanced biphasic current pulses for 450-1730 hours over implant periods of up to four months. Charge densities varied from 0.6-0.9 microC.cm-2 geom. per phase for monopolar electrodes to 12-26 microC.cm-2 geom. per phase for the bipolar electrodes. Electrically-evoked auditory brainstem responses (EABRs) were periodically monitored during stimulation to confirm that the stimulus levels were above threshold, and to monitor any change in the response of the auditory nerve. Following completion of the stimulation program cochleae were prepared for histological examination. EABRs exhibited relatively stable thresholds for both stimulated and implanted, unstimulated control cochleae for the stimulus duration. While the growth in response amplitude as a function of stimulus current remained stable for the bipolar control and monopolar stimulated cochleae, the five cochleae chronically stimulated using bipolar electrodes exhibited a moderate to large increase in response amplitude. These increases were associated with a more widespread fibrous tissue response which may have altered the current distribution within these cochleae. Implanted control cochleae exhibited significantly less tissue response within the scala tympani. Importantly, we observed no statistically significant difference in the spiral ganglion cell density associated with chronic electrical stimulation when compared with unstimulated control cochleae. While the present study supports the safe application of cochlear implants in young profoundly deafened children, it does not corroborate previous studies that have reported electrical stimulation providing a trophic effect on degenerating auditory nerve fibres.

Analysis of Variance↗

Restoration of auditory nerve synapses in cats by cochlear implants.

Congenital deafness results in abnormal synaptic structure in endings of the auditory nerve. If these abnormalities persist after restoration of auditory nerve activity by a cochlear implant, the processing of time-varying signals such as speech would likely be impaired. We stimulated congenitally deaf cats for 3 months with a six-channel cochlear implant. The device used human speech-processing programs, and cats responded to environmental sounds. Auditory nerve fibers exhibited a recovery of normal synaptic structure in these cats. This rescue of synapses is attributed to a return of spike activity in the auditory nerve and may help explain cochlear implant benefits in childhood deafness.

Acoustic Stimulation↗

Revision cochlear implantation for facial nerve stimulation in otosclerosis.

OBJECTIVE: To find if patients experiencing postsurgical facial nerve stimulation caused by underlying disease process (ie, otosclerosis) can improve their hearing performance with their cochlear implant by reimplantation and by an optimal programming strategy. DESIGN: Retrospective analysis. SETTING: Academic tertiary referral center. PATIENTS: Two cochlear otosclerosis patients with resistant facial nerve stimulation (FNS). Both patients were initially implanted with Nucleus 22 devices (Cochlear Corporation, Englewood, Colo) and they developed FNS after a period of use. Owing to the decreasing number of active electrodes, concurrent decreases in speech understanding occurred. INTERVENTIONS: Various programming approaches were used to address the FNS. Both subjects ultimately received Nucleus 24 devices. One was reimplanted in the same ear, and the other was implanted in the opposite ear. Both have been followed up for 8 months following the reimplantation. MAIN OUTCOME MEASURES: Cochlear implant programming levels, cochlear implant performance, and facial nerve stimulation. RESULTS: The FNS was managed for more than 3 years through optimized programming. However, the FNS progressed until performance dropped below acceptable levels. Reimplantation was believed to be the only option for improvement. After reimplantation and programming, both subjects showed immediate improvement in speech discrimination. One user increased his consonant-nucleus-consonant word score from 12% preoperatively to 42%, and the other's performance increased from 0% to 86%. CONCLUSIONS: Our results suggest that having more programming options with newer devices is critical in otosclerotic or ossified users who experience FNS. Also, reimplantation may be a useful tool to improve performance.

Cochlear Implantation↗

Auditory nerve terminals in the cochlear nucleus magnocellularis: differences between low and high frequencies.

Primary auditory nerve fibers were labelled in the barn owl by localized horseradish peroxidase (HRP) injections into the cochlear nucleus angularis. They were followed to their terminal sites in the hearing organ (basilar papilla), confirming that they were auditory, and to the cochlear nucleus magnocellularis. The terminal sites of low-frequency fibers within nucleus magnocellularis always included an area previously described as the lagenar part, i.e., an area receiving primary input which is probably only vestibular. Furthermore, a number of differences were recognized between these low-frequency (up to 0.64 kHz) and the high-frequency (1.8 kHz and above) auditory nerve projections to nucleus magnocellularis. Most importantly, the collaterals given off by low-frequency fibers into the nucleus typically showed multiple terminal branching, with both en passant and terminal bouton-like swellings. High-frequency fiber collaterals, in contrast, terminated unbranched in a single endbulb of Held. Nucleus magnocellularis is the first station in a brainstem auditory pathway processing stimulus timing information, coded through neuronal phase locking. The prominent difference in terminal shape found between its low- and high-frequency input fibers is interpreted as reflecting different requirements of the absolute temporal precision for significant phase locking. Terminals in the shape of endbulbs of Held are probably a specialization to improve the temporal precision of synaptic transmission, allowing phase locking to higher frequencies.

Acoustic Stimulation↗