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Synaptophysin immunoreactivity in the cat cochlear nuclei.

The presence of synaptophysin, a presynaptic Ca2+ binding glycoprotein, has been analyzed in the cochlear nucleus complex of the adult cat using an antisynaptophysin monoclonal antibody. Synaptophysin immunoreactivity was differently distributed between regions of cochlear nuclei. Terminal boutons contacting directly with neurons (cell bodies and dendrites) or in the neuropil of ventral and dorsal cochlear nuclei appeared immunostained. In the ventral cochlear nucleus, synaptophysin-labelled boutons were clearly defined in contact with spherical, globular, multipolar, octopus and cochlear-nerve root neurons. However, the dorsal cochlear nucleus showed a dense immunostained network of synaptophysin-labelled puncta, inside which some neuron cell bodies were observed. The present findings show a differential distribution of synaptophysin-immunostained boutons between the ventral and the dorsal cochlear nuclei of the cat. The present description of the different synaptophysin-labelled terminal boutons in the cochlear nuclei complex and their pattern of distribution, will be useful for further studies on development, degeneration or regeneration of the peripheral auditory pathway.

Animals↗

Do cochlear nuclei contribute to auditory lateralization? A stereological evaluation of neuron numbers.

The aim of this study was to estimate the total number of cells in the subdivisions of the cochlear nucleus (CN) of the rat with unbiased stereological methods. The total number of neurons was determined in both the ventral cochlear nucleus (VCN) and the dorsal cochlear nucleus (DCN) to compare the right and left sides. The total cell numbers were 15,280 in the left VCN, 15,400 in the right VCN, 10,260 in the left DCN, and 10,860 in the right DCN. Comparison of the right and left major subdivisions of the CN of the rat showed that there was no significant difference between the right and left sides of the rat CN. This result indicates that the CNs do not contribute to auditory lateralization in the rat in regard to cell numbers.

Animals↗

Projections to the medial superior olive from the medial and lateral nuclei of the trapezoid body in rodents and bats.

In this study we present direct evidence of axonal projections from both the medial and lateral nuclei of the trapezoid body to the medial superior olive. Projections were traced by intracellularly labeling cells and axons in a tissue slice preparation of two rodent species, Mus musculus and Meriones unguiculatus and two bat species, Eptesicus fuscus and Pteronotus parnellii. The main axon of most principal cells in the medial nucleus of the trapezoid body gives off one or more collateral branches which arborize within the medial superior olive. These collateral axons form small bouton-like swellings which primarily contact somata within the central cell column in the medial superior olive. Likewise, labeled elongate and multipolar cells of the lateral nucleus of the trapezoid body send axons to both the medial and lateral superior olives. These axons also form perisomatic contacts in both target nuclei. These two sets of projections may relay ascending input to the medial superior olive and the lateral superior olive; the medial nucleus of the trapezoid body is known to relay input from the contralateral ventral cochlear nucleus, and the lateral nucleus of the trapezoid body may relay input from the ipsilateral ventral cochlear nucleus. These projections offer two routes for indirect, possibly inhibitory input to reach the medial superior olive from both cochlear nuclei. These indirect, inhibitory pathways may parallel the direct excitatory projections the medial superior olive receives from each cochlear nucleus.

Animals↗

Effects of electrode location on speech recognition with the Nucleus-22 cochlear implant.

Speech recognition performance was measured as a function of electrode in two experiments with the Nucleus-22 cochlear implant using 4-electrode SPEAK speech processors. In experiment 1, the four stimulated electrode pairs were shifted in 0.75-mm steps over 3 mm in the apical-basal direction. In experiment 2, the four electrodes were closely spaced and positioned apically, medially, or basally. An additional condition spaced the four electrodes as widely as possible. In experiment 1, City University of New York sentence scores showed a significant decrease in performance as the electrodes were shifted basally; no other speech measures showed a significant change with electrode location. For experiment 2, all scores were the best with the processor that had the electrodes spaced as widely as possible. In both experiments, all 4-electrode SPEAK processors produced significantly poorer speech recognition than the subject's own 20-electrode processor. These results indicate that the location of electrodes is an important factor in implant performance.

Adult↗

Cortical and medullary somatosensory projections to the cochlear nuclear complex in the hedgehog tenrec.

Various tracer substances were injected into the spinal cord, the dorsal column nuclei, the trigeminal nuclear complex and the somatosensory cortex in Madagascan hedgehog tenrecs. With the exception of the cases injected exclusively into the spinal cord all injections gave rise to sparse, but distinct anterograde projections to the cochlear nuclear complex, particularly the granular cell domain within and outside of the dorsal cochlear nucleus. Among these cochlear afferents the projection from the primary somatosensory cortex is the most remarkable because the hedgehog tenrec has one of the lowest encephalisation indices among mammals and a similar cortico-cochlear connection has not been demonstrated so far in other species.

Afferent Pathways↗

Fast axonal transport in auditory neurons of the guinea pig: a rapidly turned-over glycoprotein.

Proteins of the fast component of axonal transport were analyzed by one- and two-dimensional polyacrylamide gel electrophoresis in the guinea pig spiral ganglion, which has its cell bodies in the cochlea and its axons in the eighth cranial nerve projecting to the ipsilateral cochlear nucleus. We found that we could easily identify the proteins of the fast component even though these axons are only about 3 mm long because the cochlea minimized diffusion of labeled precursor into the cochlear nucleus. The composition of the fast component of the spiral ganglion cells was similar, but not identical, to the fast component of guinea pig retinal ganglion cells. One difference was the predominance in the spiral ganglion cell fast component of a rapidly turned-over glycoprotein (RTGP) with a molecular weight of 110,000-140,000 and an isoelectric point of 5.0 RTGP accumulated in the cochlear nucleus for just the first 3 hr after the application of the labeled precursor and then rapidly disappeared, whereas the other major fast component polypeptides continued to accumulate for 12-24 hr. RTGP was also tentatively identified in the fast component of retinal ganglion cells, but was not as prominently labeled relative to the other fast-component proteins in those cells. The rapid disappearance of RTGP from spiral ganglion cell terminals in the cochlear nucleus may be a result of secretion, perhaps as part of a synaptic vesicle, or retrograde transport as a feedback signal. The difference in the relative amounts of RTGP found in spiral ganglion and retinal ganglion cell terminals may reflect differences in the fundamental properties of the two groups of neurons.

Animals↗

Central physiological correlates of ageing and presbycusis in mice.

Responses of neurons in the central auditory system of ageing mice suggest several sources of age-related problems in hearing. The central representation of frequency (tonotopic organization) is disrupted in mice with presbycusis, implying a cause of problems with frequency coding. In very old mice with only minimal hearing loss, normal-responding neurons co-exist with "sluggish" neurons, which suggests there is a process of attrition that affects some neurons more than others. Spontaneous activity increases in neurons of older mice, implying a decrease in the physiological signal-to-noise ratio. The effects of age-related hearing loss are more severe in the ventral cochlear nucleus than in the dorsal cochlear nucleus, suggesting that various functional circuits may be more or less vulnerable to presbycusis.

Acoustic Stimulation↗

The use of averaged electrode voltages to assess the function of nucleus internal cochlear implant devices in children.

Averaged electrode voltages (AEVs) provide an objective measure of the output of the Nucleus multichannel cochlear implant device. AEVs are the peak-to-peak voltages of each electrode in the internal array and are recorded from electrodes placed on the scalp. This article summarizes average voltage data for 25 children with complete insertions of the electrode array. Data are compared with previously published adult data and are evaluated based on the location of the recordings (clinic versus operating room). AEV data can be applied clinically to identify implant problems. AEV recordings for this purpose are particularly important with children who may not be able to provide accurate reports of implant function. Case studies are presented to illustrate the application of the AEV procedure to examine implant malfunction in six children.

Adolescent↗

Medical or surgical complications related to the Nucleus multichannel cochlear implant.

A questionnaire was sent to 152 surgeons to survey complications associated with the implantation of the Nucleus multichannel cochlear implant. Complications were categorized as life-threatening; major, if they necessitated revision surgery; or minor, if they resolved spontaneously or with minimal treatment. A total of 55 complications occurred in 459 reported operations for an overall complication rate of 11.8%. There were no deaths, but there was one life-threatening complication, a case of meningitis. There were 23 (4.8%) major complications, most of which involved flap design or electrode insertion (and included the case of meningitis). There were 32 (7%) minor complications. Most of the complications might have been avoided by proper training, planning of the operations, and careful attention to detail. We recommend that all prospective implant surgeons attend a device-specific training course and practice in the temporal bone laboratory.

Cochlear Implants↗

Distribution of HCN1 and HCN2 in rat auditory brainstem nuclei.

Auditory brainstem neurons that are involved in the precise analysis of the temporal pattern of sounds have ionic currents activated near the resting potential to shorten membrane time constants. One of these currents is the hyperpolarization-activated current (Ih). Molecular cloning of the channels underlying Ih revealed four different isoforms (HCN1-4). HCN1 and HCN2, which are widely distributed in the brain, differ in their activation kinetics, voltage dependence and sensitivity to cAMP. We determined the distribution of the HCN1 and HCN2 isoform in the auditory brainstem and midbrain of young rats (P20-30), using standard immunohistochemical techniques. HCN1 antibodies gave rise to punctate staining on the somatic and dendritic membrane. Strong HCN1 staining was present on octopus and bushy cells of the ventral cochlear nucleus, principal neurons of the lateral and medial superior olive, and neurons of the ventral nucleus of the lateral lemniscus. No HCN1 staining was observed in the dorsal cochlear nucleus and the medial nucleus of the trapezoid body (MNTB). In contrast, HCN2 staining was strongest in the MNTB and the dorsal nucleus of the lateral lemniscus. Strong HCN2 antibody labelling was also observed in bushy cells of the ventral cochlear nucleus. In the central nucleus of the inferior colliculus only a subpopulation of neurons showed HCN1 or HCN2 immunolabelling. This differential distribution of HCN1 and HCN2 channels is in agreement with the physiologically observed Ih currents in corresponding neuronal populations and might represent the basis for functional heterogeneity and diverse sensitivity to neuromodulators.

Animals↗

Sources of input to the cochlear granule cell region in the guinea pig.

Anterograde and retrograde transport of fluorogold was used to trace input to the superficial granule cell layer of the ventral cochlear nucleus in the guinea pig. Infusion of fluorogold into the labyrinth resulted in heavy labeling of eighth nerve axons and their terminals in the ventral cochlear nucleus, but only a few labeled axons entered the granule cell layer. Injections of fluorogold restricted to the granule cell layer retrogradely labeled neurons in the ipsilateral lateral superior olivary nucleus, in the periolivary region predominantly contralaterally, and in the inferior colliculus predominantly ipsilaterally. Labeled neurons were also present in the ipsilateral ventral cochlear nucleus, but this may be due to interruption of axons of passage in the lateral ventrotubercular tract. Overall this study demonstrates very restricted direct cochlear input to the granule cell region, but provides evidence for projections from several brainstem auditory nuclei.

Animals↗

Acoustic chiasm II: Anatomical basis of binaurality in lateral superior olive of cat.

The afferent projections to the lateral superior olive (LSO) were examined with horseradish peroxidase, horseradish peroxidase-wheat germ agglutinin conjugate, 125I-wheat germ agglutinin and tritiated leucine autoradiograhy, anterograde axonal degeneration, and 14C-2-deoxyglucose methods. The pathway to the ipsilateral LSO orginates in the spherical cells in anteroventral cochlear nucleus. Although some of the fibers pass above the lateral nucleus of the trapezoid body, most pass below it and turn at right angles to enter the LSO either directly through its ventral, lateral, or dorsal borders, or through its ventral or dorsal hilus. They end in unpolarized terminal fields throughout the LSO. Most if not all of these fibers are true collaterals of axons continuing across the midline in the trapezoid body. Verifying Held's (1893) finding of a major direct projection from the cochlear nucleus to the contralateral medial nucleus of the trapezoid body (MTB) and Rasmussen's ('46) finding of a major projection from the MTB to the LSO, the present results illustrate that this two-neuron pathway probably supplies all but a very small component of the relatively direct input to the LSO from the contralateral ear. This pathway originates in the globular cells of the ventral cochlear nucleus and relays mostly though not exclusively through the "principal cells" in the more rostral parts of the MTB. It terminates mostly in perisomal endings in unpolarized fields throughout the LSO, though most heavily within the (high frequency) medial and middle limbs and less heavily in the LSO's (low frequency) lateral limb. In addition to this indirect pathway, there is a small direct pathway to the contralateral LSO as suggested by Goldberg and Brown ('69) and Warr ('72, '82). This direct pathway to the contralateral LSO, like the direct ipsilateral pathway, probably originates in the spherical cell region of the ventral cochlear nucleus, crosses the midline in the trapezoid body, and terminates in a small circumscribed area within the LSO's ventromedial (high frequency) area. The 2-deoxyglucose method applied to cats in which the ipsilateral and contralateral pathways have been surgically isolated shows that each of the pathways converging on the LSO is topographically and tonotopically organized with the ipsilateral and the combined contralateral terminations in strict tonotopic register.

Animals↗

Ectopic Purkinje cells in the adult rat: olivary innervation and different capabilities of migration and development after grafting.

The abnormal location of large numbers of neurones is characteristic of genetic mutations which impair the migratory processes of developing nerve cells. Nevertheless, the presence of small amounts of ectopic neurones is a fairly common finding even in normal adult animals. The first aim of this study was to investigate a series of features of ectopic Purkinje cells in normal adult rats and particularly to assess whether these cells are still capable of interacting with their normal afferents. Several displaced Purkinje cells, identified by anti-D28k calbindin immunolabelling as well as by typical morphological features, were present in the brainstem and cerebellum of all the examined animals. Two distinct morphological types of such cells could be recognized: 1) noncortical Purkinje cells, located in several areas of the dorsal brainstem and cerebellum, characterised by poorly developed and randomly oriented dendrites; and 2) cortical Purkinje cells, exclusively located in the dorsal cochlear nucleus, characterised by large dendritic trees oriented along parasagittal planes. Tracing experiments, in which Phaseolus vulgaris leucoagglutinin (PHA-L) was injected into the inferior olive, revealed that several ectopic Purkinje cells, belonging to both types, were contacted by the terminal arbours of olivary axons, structurally similar to cerebellar climbing fibres. On the basis of the observation that ectopic Purkinje cells were more frequent in the dorsal cochlear nucleus than in any other of the examined regions, we tested the hypothesis that this nucleus might represent a particularly favourable environment for the survival and development of Purkinje cells. By grafting embryonic cerebellar tissue in the fourth ventricle, only minimal migration of Purkinje cells into the recipient parenchyma was observed when the transplant was placed on the brainstem surface caudal to the cochlear nucleus. By contrast, when the graft was apposed to the latter nucleus, large numbers of Purkinje cells migrated and developed in its superficial layers. These Purkinje cells passed through all the different phases which characterise the normal ontogenesis of this neuronal population and finally developed mature structural features similar to those displayed by cortical ectopic Purkinje cells. This study demonstrates that at least some of the ectopic Purkinje cells receive their physiological olivary input. This fact indicates that Purkinje cells are able to attract olivary axons and establish specific connections, even if they are displaced in an abnormal environment. In addition, we show that the dorsal cochlear nucleus represents a particularly favourable environment for the survival and the development of Purkinje cells.

Animals↗

[Anatomical references in auditory brainstem implant surgery].

UNLABELLED: The auditory brainstem implant (ABI) is an option for deaf patients who do not have the whole of their auditory pathways preserved. The surgery, because of its anatomical and functional complexity, requires specific training of the surgeon in an anatomy lab. AIM: To study the surgical anatomy of the surgery for auditory brainstem implant. STUDY DESIGN: Anatomic study. MATERIAL AND METHOD: In this exercise we dissected a fresh cadaver prepared with a dye solution injected into the arteries and intra-cranial veins. The location for the insertion of the electrode for the ABI has been studied through the translabyrinthine access. RESULTS: The surgical technique used for implanting the electrode of the brainstem is similar to that used in the removal of the schwannoma vestibular. The cochlear nucleus complex, composed of the ventral and dorsal cochlear nuclei is the location for placing the electrode. The ventral cochlear nucleus is the principal nucleus for transmission of neural impulses from the VIII par and form the main ascendant route of the cochlear nerve. Neither the ventral nor the dorsal nuclei are visible during surgery and their location depends on the identification of adjacent anatomical structures. CONCLUSION: The region for the implantation of the electrode in the auditory brainstem implant presents anatomical references that allow its easy identification during surgery.

Auditory Brain Stem Implants↗

Preliminary experience with neural response telemetry in the nucleus CI24M cochlear implant.

OBJECTIVE: This study aimed to compare recordings of the electrically evoked whole nerve action potential (EAP) made using the reverse telemetry system of the Nucleus CI24M device with those recorded from individuals who use the Ineraid cochlear implant system. STUDY DESIGN: Data were collected in a prospective fashion from Nucleus CI24M cochlear implant users and compared with retrospective data collected from patients who use the Ineraid device. SETTING: All data were collected at the Department of Otolaryngology-Head and Neck Surgery, University of Iowa Hospitals and Clinics. PATIENTS: Data are reported from 8 patients who use the Nucleus CI24M cochlear implant and 20 patients who use the Ineraid cochlear implant system. INTERVENTIONS: The interventions described in this study were diagnostic in nature. MAIN OUTCOME MEASURES: EAP growth and refractory recovery data are reported. EAP thresholds recorded from patients who use the Nucleus CI24M device also are compared with behavioral thresholds for the stimulus used to evoke the EAP as well as the stimulation levels needed to program the speech processor. RESULTS: EAP morphology, growth, and refractory recovery functions recorded using the Nucleus CI24M reverse telemetry system compared favorably with similar measures recorded from Ineraid cochlear implant users. CONCLUSIONS: Reasonable EAP responses can be recorded using the Nucleus CI24M device. More data are needed to determine whether the information about neural responsiveness available with this device will be clinically useful.

Cochlear Implantation↗

GABAergic neurons and axon terminals in the brainstem auditory nuclei of the gerbil.

The anatomical localization of glutamic acid decarboxylase (GAD), the synthesizing enzyme for GABA, was analyzed in the brainstem auditory nuclei of the adult gerbil. GAD-positive terminals and somata were present in the cochlear nucleus, superior olivary complex, lateral lemniscus, and inferior colliculus in varying concentrations and patterns. One of the highest densities of GAD-positive terminals is found in the superficial layers of the dorsal cochlear nucleus (DCN), whereas the ventral cochlear nucleus (VCN) has somewhat fewer terminals that are arranged in pericellular plexuses. GAD-positive neurons occur mainly in the superficial and fusiform layers of the DCN and are scattered throughout the VCN. Within the superior olivary complex, the highest concentration of immunoreactive terminals and neurons occurs in the ventral and lateral nuclei of the trapezoid body. In contrast, the medial nucleus of the trapezoid body and the medial superior olive contain fewer GAD-positive puncta and probably no immunoreactive somata. The lateral superior olive and superior periolivary nucleus contain a few immunoreactive puncta but a large number of immunoreactive somata. In the midbrain, the nuclei of the lateral lemniscus contain a moderate number of GAD-positive puncta and a large number of different types of GAD-positive neurons. The inferior colliculus also contains a heterogeneous population of labeled somata, most of which are multipolar neurons. In addition, a high concentration of immunoreactive puncta occurs in this region. These data demonstrate a diverse distribution of GAD-positive neurons and puncta throughout the brainstem auditory nuclei and suggest that GABA might be an important neurotransmitter in the processing of auditory information.

Animals↗

Effects of dynamic range and amplitude mapping on phoneme recognition in Nucleus-22 cochlear implant users.

OBJECTIVE: To determine the consequences for phoneme recognition of errors in setting threshold and loudness levels in cochlear implant listeners using a 4-channel continuous interleaved sampling (CIS) speech processor. DESIGN: Three Nucleus-22 cochlear implant listeners, who normally used the SPEAK speech processing strategy participated in this study. An experimental 4-channel CIS speech processor was implemented in each listener as follows. Speech signals were band-pass filtered into four broad frequency bands and the temporal envelope of the signal in each band was extracted by half-wave rectification and low-pass filtering. A power function was used to convert the extracted acoustic amplitudes to electric currents. The electric currents were dependent on the exponent of the mapping power function and the electrode dynamic range, which was determined by the minimum and maximum stimulation levels. In the baseline condition, the minimum and maximum stimulation levels were defined as the psychophysically measured threshold level (T-level) and maximum comfortable level (C-level). In the experimental conditions, the maximum stimulation levels were fixed at the C-level and the dynamic range (in dB) was changed by varying the minimum stimulation levels on all electrodes. This manipulation simulates the effect of an erroneous measurement of the T-level. Phoneme recognition was obtained as the dynamic range of electrodes was changed from 1 dB to 20 dB and as the exponent of the power-law amplitude mapping function was changed from 0.1 to 0.4. RESULTS: For each mapping condition, the electric dynamic range had a significant, but weak effect on vowel and consonant recognition. For a strong compression (p = 0.1), best vowel and consonant scores were obtained with a large dynamic range (12 dB). When the exponent of the mapping function was changed to 0.2 and 0.4, the dynamic range producing the highest scores decreased to 6 dB and 3 dB, respectively. CONCLUSIONS: Phoneme recognition with a 4-channel CIS strategy was only mildly affected by large changes in both electric threshold and loudness mapping. Errors in threshold by a factor of 2 (6 dB) and in the loudness mapping exponent by a factor of 2 were required to produce a significant decrease in performance. In these extreme conditions, the effect of the electric dynamic range on phoneme recognition could be due to two independent factors: abnormal loudness growth and a reduction in the number of discriminable intensity steps. The decrease in performance caused by a reduced electric dynamic range can be compensated by a more expansive power-law mapping function, as long as the number of discriminable intensity steps is moderately large (e.g., >8).

Acoustic Stimulation↗

AutoNR: an automated system that measures ECAP thresholds with the Nucleus Freedom cochlear implant via machine intelligence.

OBJECTIVE: AutoNRT is an automated system that measures electrically evoked compound action potential (ECAP) thresholds from the auditory nerve with the Nucleus Freedom cochlear implant. ECAP thresholds along the electrode array are useful in objectively fitting cochlear implant systems for individual use. This paper provides the first detailed description of the AutoNRT algorithm and its expert systems, and reports the clinical success of AutoNRT to date. METHODS: AutoNRT determines thresholds by visual detection, using two decision tree expert systems that automatically recognise ECAPs. The expert systems are guided by a dataset of 5393 neural response measurements. The algorithm approaches threshold from lower stimulus levels, ensuring recipient safety during postoperative measurements. Intraoperative measurements use the same algorithm but proceed faster by beginning at stimulus levels much closer to threshold. When searching for ECAPs, AutoNRT uses a highly specific expert system (specificity of 99% during training, 96% during testing; sensitivity of 91% during training, 89% during testing). Once ECAPs are established, AutoNRT uses an unbiased expert system to determine an accurate threshold. Throughout the execution of the algorithm, recording parameters (such as implant amplifier gain) are automatically optimised when needed. RESULTS: In a study that included 29 intraoperative and 29 postoperative subjects (a total of 418 electrodes), AutoNRT determined a threshold in 93% of cases where a human expert also determined a threshold. When compared to the median threshold of multiple human observers on 77 randomly selected electrodes, AutoNRT performed as accurately as the 'average' clinician. CONCLUSIONS: AutoNRT has demonstrated a high success rate and a level of performance that is comparable with human experts. It has been used in many clinics worldwide throughout the clinical trial and commercial launch of Nucleus Custom Sound Suite, significantly streamlining the clinical procedures associated with cochlear implant use.

Algorithms↗