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Functional anatomy of the human cochlear nerve and its role in microvascular decompressions for tinnitus.

OBJECTIVE: The functional anatomy (i.e., tonotopy) of the human cochlear nerve is unknown. A better understanding of the tonotopy of the central nervous system segment of the cochlear nerve and of the pathophysiology of tinnitus might help to ameliorate the disappointing results obtained with microvascular decompressions in patients with tinnitus. METHODS: We assume that vascular compression of the cochlear nerve can induce a frequency-specific form of hearing loss and that when the nerve is successfully decompressed, this hearing loss can recuperate. Thirty-one patients underwent a microvascular decompression of the vestibulocochlear nerve for vertigo or tinnitus. Preoperative audiograms were subtracted from postoperative audiograms, regardless of the surgical result with regard to the tinnitus and vertigo, because the hearing improvement could be the only sign of the vascular compression. The frequency of maximal improvement was then correlated to the site of vascular compression. A tonotopy of the cochlear nerve was thus obtained. RESULTS: A total of 18 correlations can be made between the site of compression and postoperative maximal hearing improvement frequency when 5-dB hearing improvement is used as threshold, 13 when 10-dB improvement is used as threshold. A clear distribution can be seen, with clustering of low frequencies at the posterior and inferior side of the cochlear nerve, close to the brainstem, and close to the root exit zone of the facial nerve. High frequencies are distributed closer to the internal acoustic meatus and more superiorly along the posterior aspect of the cochlear nerve. CONCLUSION: The tonotopic organization of the cisternal segment of the cochlear nerve has an oblique rotatory structure as a result of the rotatory course of the cochlear nerve in the posterior fossa. Knowledge of this tonotopic organization of the auditory nerve in its cisternal course might benefit surgeons who perform microvascular decompression operations for the vestibulocochlear compression syndrome, especially in the treatment of unilateral severe tinnitus.

Adult↗

Cochlear nerve projections to the small cell shell of the cochlear nucleus: the neuroanatomy of extremely thin sensory axons.

Labeling cochlear nerve fibers in the inner ear of chinchillas with biotinylated dextran polyamine was used to trace the thin fibers (Type II), which likely innervate outer hair cells. These axons, 0. 1-0.5 microm in diameter, were distinguished from the thicker Type I, fibers innervating inner hair cells, and traced to small-cell clusters in the cochlear nucleus. This study provided two major new insights into the outer hair cell connections in the cochlear nucleus and the potential significance of very thin axons and synaptic nests, which are widespread in the CNS. 1) EM serial reconstructions of labeled and unlabeled material revealed that Type II axons rarely formed synapses with conventional features (vesicles gathered at junctions). Rather, their endings contained arrays of endoplasmic reticulum and small spherical vesicles without junctions. 2) Type II axons projected predominantly to synaptic nests, where they contacted other endings and dendrites of local interneurons (small stellate and mitt cells, but not granule cells). Synaptic nests lacked intrinsic glia and, presumably, their high-affinity amino acid transporters. As functional units, nests and their Type II inputs from outer hair cells may contribute to an analog processing mode, which is slower, more diffuse, longer-lasting, and potentially more plastic than the digital processors addressed by inner hair cells.

Animals↗

Effect of compression on the cochlear nerve: a short- and long-term electrophysiological and histological study.

The short- and long-term effects of static compression of the cochlear nerve were studied in dogs. The nerve was exposed in the cerebellopontine angle and a modified aneurysm clip was applied to reduce the diameter of the nerve trunk to 50%, 40%, 30% or 20% of normal (designated respectively as 50%, 60%, 70%, and 80% compression). Brainstem auditory evoked potentials (BAEPs) were monitored intraoperatively and post-operatively. The animals were sacrificed between 5 and 119 days after nerve compression and temporal bones were examined histologically. In the 50% compression group, all peaks except peak I disappeared immediately after nerve compression. After release of the clip, however, peak II and subsequent components recovered and prolonged interpeak latency (IPL) between peaks I and IV normalized within 7 days. In the 60% compression group, recovery was incomplete for as long as 49 days after compression. Significant histological changes were not always reflected in the electrophysiological recordings, as shown by the finding of multiple cavitations at the compressed portion of the cochlear nerve in cases in which conduction block of cochlear nerve impulses was reversible. In the 70% compression group, peak IV did not reappear for more than 1 week, and histological examination revealed severe damage to all cochlear nerve fibers except those from the apical turn, which lie in the center of the cochlear nerve trunk. Severe injury occurred to the cochlear nerve fibers that are situated more superficially in the nerve, which are tonotopically responsible for the perception of high-frequency sound and the generation of BAEPs. This means that the BAEP changes due to cochlear nerve compression would be detectable by BAEP monitoring, although changes in the apical region of the cochlea are not fully detectable by BAEP monitoring. In the 80% compression group, all peaks except peak I were lost permanently and the amplitude of peak I, which had been preserved in the acute phase, gradually decreased. Reversibility of impaired cochlear nerve impulse conduction was related to the severity of compression, and at some level of compression between 70% and 80% the nerve fibers generating BAEPs permanently lost the ability to conduct electrical impulses proximal to the site of compression. In the 70% and 80% compression groups, the amplitude of peak I gradually decreased over the first 30 days after compression and did not change significantly thereafter. Histologically, the branches of the internal auditory artery were resilient to compression, although they are easily avulsed due to stretch force. Furthermore, retrograde degeneration of cochlear neurons triggered by compression at the cisternal portion of the cochlear nerve was apparent. Such slowly progressive degeneration of nerve fibers may play a part in development of the delayed postoperative hearing disturbance.

Animals↗

[Pathophysiology of cochlear nerve injury incurred through surgical manipulation in the cerebellopontine angle. Scanning electron microscopic observations].

Cochlear nerve injuries caused by surgical manipulation in the cerebellopontine (CP) angle were electrophysiologically and morphologically investigated in dogs. Operative procedures similar to those performed in the CP angle in humans were performed. Lateral-to-medial retraction of the cerebellar hemispheres applied traction force to the cochlear nerve. Brainstem auditory evoked potentials and compound action potentials from the intracranial portions of the cochlear nerves were recorded during the procedures. As a result of the traction force produced by manipulations in the CP angle, the Schwann-glial junctions of the cochlear nerve were separated in some dogs. The exit portions of the cochlear nerve fibers and the branches of the internal auditory artery from the tractus spiralis foraminosus at the fundus of the internal auditory canal. This finding may explain occasional occurrence of postoperative high frequency hearing loss among patients who undergo surgical manipulation in the CP angle. In some cases, massive hemorrhage and exudation of plasma were observed in the deep portion of the modiolus, where they compressed the cochlear nerve trunk. This is apparently one of the causes of intraoperative failure of cochlear function. In this study, no correlations between electrophysiological and morphological findings were established.

Action Potentials↗

Acoustic neuroma surgery: use of cochlear nerve action potential monitoring for hearing preservation.

OBJECTIVES: To compare the hearing preservation results obtained with use of two intraoperative eighth nerve monitoring methods, cochlear nerve action potential (CNAP) and auditory brainstem response (ABR), during complete acoustic neuroma (AN) resection. STUDY DESIGN: Retrospective. SETTING: Tertiary referral center. PATIENTS: Thirty-three consecutive patients who underwent hearing preservation AN surgery. INTERVENTIONS: Intraoperative monitoring by CNAP and/or ABR during AN resection. MAIN OUTCOME MEASURE: Postoperative hearing. Hearing preservation was considered achieved for pure-tone average < or =50 dB and speech discrimination > or =50%. RESULTS: Thirty-two patients met inclusion criteria for the study. Monitoring was successfully performed in 23 of 25 patients (92%) who underwent attempted CNAP monitoring and 13 of 27 (48%) who underwent attempted ABR monitoring. When tumor size was < or =20 mm in greatest dimension, hearing preservation was achieved in 12 of 18 patients (67%) monitored with CNAP, versus 2 of 8 patients (25%) not monitored with CNAP (p = 0.05). Monitoring by ABR did not improve hearing preservation rates compared with those not monitored with ABR (40% vs. 63%). At the completion of surgery, the presence or absence of CNAP predicted the presence or absence of hearing preservation in 18 of 23 cases (p = 0.01), while ABR successfully predicted hearing results in 10 of 13 cases (p = 0.05). CONCLUSIONS: When CNAP and ABR monitoring techniques during AN surgery were compared, CNAP was more frequently obtainable. Monitoring by CNAP was significantly associated with a higher chance of hearing preservation. Monitoring by ABR did not have a positive influence on hearing preservation results. Both ABR and CNAP were useful for predicting postoperative hearing.

Adult↗

The cochlear nerve in various forms of deafness.

Operative specimens of cochlear nerve of 56 patients with profound deafness of varying origin were examined under the light microscope and the number of myelinated nerve fibers in each specimen was counted. The transverse fascicular area of each nerve was also determined. When the resulting neuron populations were evaluated with regard to the cochlear implant program the only truly unsuitable ears for artificial stimulation were found to be those with cholesteatoma involving the cochlear nerve and ears with local pathology in the internal auditory canal severe enough to cause atrophy of the cochlear nerve.

Adult↗

Electrode independence in intraneural cochlear nerve stimulation.

OBJECTIVES/HYPOTHESIS: We have previously reported feline electrophysiological and anatomical studies focused on the development of an intraneural auditory neuroprosthesis. Because only the tips of the electrodes implanted in the cochlear nerve are the stimulating elements that abut the nerve axons, we hypothesize that intraneural stimulation will be highly focal in nature. In this article, we report the electrophysiological characterization of the selective activation of subpopulations of cochlear nerve fibers via electrodes implanted in feline cochlear nerve. STUDY DESIGN: We have used a forward-masking paradigm to estimate the extent of stimulation overlap produced by pairs of electrodes implanted into the cochlear nerve. METHODS: The technique uses sequential stimulation via masking and probe electrodes and monitoring of the electrically evoked auditory brain stem response as an index of cochlear nerve fiber recruitment. We investigated overlap in all possible electrode pair combinations. RESULTS AND CONCLUSION: Many electrode pairs manifest virtually no overlap in the subpopulations of fibers excited by perithreshold stimuli, whereas most had considerable overlap at higher stimulation levels. However, we also noted that our measured overlap was similar across electrodes possibly because of lack of specificity of the whole nerve electrically evoked auditory brain stem response as an assay for this parameter. These findings indicate that direct cochlear nerve stimulation via intraneural electrodes provides selective excitation of small subpopulations of cochlear nerve fibers, and suggest that cochlear nerve stimulation may selectively evoke narrow-band frequency percepts.

Animals↗

Cochlear nerve stimulation with a 3-dimensional penetrating electrode array.

HYPOTHESIS: An array of penetrating microelectrodes can be implanted into the cochlear nerve to produce stable evoked responses with important electrophysiologic advantages over conventional electrode technology. BACKGROUND: A totally implantable cochlear implant system would benefit from new electrode technology that lowers the current required for stimulation. Modern cochlear implant arrays placed in the scala tympani have an appreciable distance between the electrodes and the cochlear nerve, the site of intended stimulation. This distance can create the problem of cross-talk, limiting the number of electrodes that can represent discrete frequencies over a given length as well as significantly increasing stimulation thresholds and producing nonfocal stimulation of the fibers in the nerve. An electrode in direct contact with neurons in the cochlear nerve could reduce these problems. The Utah Electrode Array is a novel, three-dimensional, penetrating electrode array intended for direct neural stimulation with the potential ability to implant up to 200 electrodes directly into the cochlear nerve. METHODS: Arrays containing 6 to 19 electrodes were implanted acutely into six separate cat cochlear nerves for analysis. Thresholds and input/output functions were measured with electrically induced auditory brainstem responses. RESULTS: Current injections in 38 of 70 implanted electrodes produced stable brainstem responses after implantation. The median threshold was 15 microA. CONCLUSIONS: An array of penetrating electrodes can be implanted into the cochlear nerve and used to evoke brainstem responses. The responses are of low threshold and are stable. Arrays of electrodes, inserted into auditory nerve, could form the neural interfaces for the next generation of auditory prostheses.

Animals↗

Dependence of discharge rate on sound pressure level in cochlear nerve fibers of the alligator lizard: implications for cochlear mechanisms.

1. Rate-level functions for individual cochlear nerve fibers of the alligator lizard, Gerrhonotus multicarinatus, were generated by measuring a fiber's driven discharge rate (the difference between the average discharge rates in the presence and absence of a tone burst) as a function of sound pressure level. 2. When plotted in double logarithmic coordinates, the rate-level function approaches a straight line at low sound pressure levels and saturates at high levels. Thus the rate-level function is a saturating power function of sound pressure. We developed an algorithm to estimate the exponent of the straight-line portion of the function. When tested on simulated data with known parameters, the algorithm provided unbiased estimates of the exponent. 3. Nerve fibers innervating two distinct regions of the alligator lizard's auditory organ, the free-standing region and the tectorial region, have differing rate-level functions. 4. The mean exponent estimate of the rate-level functions of fibers innervating the free-standing region is approximately 2 at all frequencies. For stimulus frequencies at the characteristic frequency (CF), the mean value was 2.1 +/- 0.10 (SE, n = 131). For stimulus frequencies above and below CF, the mean exponent estimates were 2.1 +/- 0.13 (n = 49) and 2.1 +/- 0.11 (n = 34), respectively. A value of 2 is expected for a broad class of nonlinear systems. 5. The mean exponent estimates of the rate-level functions of fibers innervating the tectorial region were 3.0 +/- 0.30 (n = 32) for stimulus frequencies at CF, 2.5 +/- 0.33 (n = 3) for stimulus frequencies below CF, and 1.0 +/- 0.21 (n = 16) for stimulus frequencies above CF. Both the deviation from square-law behavior at CF and the frequency dependence of the exponent imply that nonlinear processing in the tectorial region differs intrinsically from that in the free-standing region. 6. For free-standing fibers, the saturation rate of the rate-level function (the maximum driven rate) is independent of stimulus frequency. This suggests that, in the free-standing region, 1) the alternating (AC) component of the receptor potential makes no significant contribution to the average rate of discharge and 2) neural saturation results from a process that occurs after the narrow-band frequency-selective process(es). 7. In tectorial fibers, the saturation rate is a bandpass function of sound frequency, with a broad peak between 150 and 300 Hz. This function appears to be common to all tectorial fibers.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

Hearing habilitation with auditory brainstem implantation in two children with cochlear nerve aplasia.

Patients with aplasia and hypoplasia of the cochlear nerve have no chance of having their hearing restored by stimulating the periphery of the auditory system using the traditional cochlear implant. A possible approach to auditory rehabilitation may be direct electrical stimulation of the cochlear nuclei with an auditory brainstem implant (ABI). Recently, two children, aged 4 and 3 years, respectively, with bilateral severe cochlear malformations and cochlear nerve aplasia received an ABI. The present paper reports the technique and the preliminary results of this experience. The classic retrosigmoid approach was used. The correct position of the electrodes was estimated with the aid of EABRs and neural response telemetry (NRT). No postoperative complications were observed. High-resolution CT scans with a bone algorithm reconstruction technique were taken postoperatively to evaluate electrode placement before discharge. The ABI was activated 30 days after implantation in both patients. To date 16 and 13 electrodes, respectively, have been activated in the two children. Three months after activation the first patient had achieved good environmental sound awareness, good speech detection and some speech discrimination. The second child, 1 month after activation, had achieved good environmental sound awareness and moderate speech detection. To the best of our knowledge this is the first report of patients with hypoplasia of the cochlea and aplasia of the cochlear nerve, aged below 5 years and treated with an ABI.

Audiometry↗

Retrograde degeneration of the cochlear nerve.

Retrograde degeneration of the cochlear neurons has been studied in different types and degrees of peripheral cochlear damage such as acoustic trauma, intoxication, heredodegenerative deafness and others. It starts only when the peripheral dendrites to the inner hair cells are irreversibly damaged. About 10% of the neurons are not affected by retrograde degeneration. They correspond to the type II and III neurons, which also survive after transection of the cochlear nerve and are mainly associated with the outer hair cells. Cochlear damage due to vascular impairment usually leads to a complete loss of cochlear neurons. In hereditary abiotrophic deafness, neuronal degeneration is slower and its extent varies considerably according to the various genetic syndromes.

Animals↗

Artificial activation and degeneration of the cochlear nerve in guinea pigs.

Degeneration of the cochlear nerve was produced in guinea pigs after treatment with high doses of ototoxic antibiotics completely destroying the cochlear receptor. An effective electric stimulation of the inner ear inducing evoked potentials at the auditory cortex was applied over a period of 3.5 months in half of the animals, while the other half was kept for control. The artificial stimulation had no effect on the sensitivity of the inner ear to electric stimulation and did not modify the extent of degeneration of the cochlear nerve.

Amikacin↗

Intraoperative monitoring of facial and cochlear nerves during acoustic neuroma surgery.

The likelihood of successful preservation of facial and cochlear nerve function during acoustic neuroma surgery has been improved by the advent of intraoperative monitoring techniques. The facial nerve is monitored by recording EMG from facial muscles, with no muscle relaxants used; mechanical irritation of the nerve during surgery causes increased EMG activity, which can be detected in real time using a loudspeaker. Brief episodes of activity associated with specific surgical maneuvers aid the surgeon in avoiding damage to the nerve, whereas prolonged tonic EMG activity may reflect significant neural injury. Electrical stimulation with a hand-held probe elicits evoked EMG responses, which can be used to locate and map the nerve in relation to the tumor. The threshold for eliciting evoked EMG responses provides a rough indicator of the functional status of the nerve. Different nerves in the posterior fossa (trigeminal, facial, spinal accessory) can be identified in multichannel recordings by the spatial distribution and latency of responses to electrical stimulation. The ability to elicit EMG responses from low amplitude stimulation of the facial nerve at the brain stem after tumor removal is a reasonable predictor of postoperative facial function. Cochlear nerve function is assessed by recording the ABR from ear canal and scalp electrodes or the CNAP with an electrode placed directly on the nerve at the brain stem root entry zone. The ABR is a well-known, noninvasive technique that can be adapted to intraoperative use relatively easily but is of limited utility owing to the delay inherent in signal averaging. Direct CNAP recordings require placement of an intracranial electrode in such a way as to contact the cochlear nerve without interfering with surgical access but have the distinct advantage of rapid feedback on changes in cochlear nerve status.

Cochlear Nerve↗

The neuronal architecture of the anteroventral cochlear nucleus of the cat in the region of the cochlear nerve root: electron microscopy.

We have studied the posterior division of the anteroventral cochlear nucleus, where the cochlear nerve root enters the brain, in the cat. In Nissl preparations, this region contains two types of neuronal cell bodies: globular and multipolar. The two types can be identified in the electron-microscope by comparing Nissl substance and rough endoplasmic reticulum. Globular cell bodies receive many synaptic terminals, which cover 85% of the surface. In contrast, multipolar cell bodies are almost entirely wrapped by thin glial sheets--synaptic terminals contact less than 15% of the surface and tend to cluster at the bases of dendrites. Synaptic terminals are of three kinds, types 1, 2, and 3, which contain large round, small round-to-oval, and small flattened synaptic vesicles, respectively. Terminals of all three kinds synapse on both types of cell bodies. However, only globular cell bodies receive the largest type 1 terminals, which correspond to end-bulbs, seen in Golgi impregnations to arise from cochlear nerve axons. Cochlear ablation leads to degeneration of type 1, but not type 2 or 3 terminals. We conclude that neurons with globular cell bodies receive heavy somatic input from the cochlear nerve, as well as from other sources. Neurons with multipolar cell bodies receive very little input to their perikarya--giving their dendrites a more important role in determining their response properties. We suggest a morphological basis for correlating individual kinds of neurons with certain electrophysiological response types.

Animals↗

Cochlear nerve size evaluation in children with sensorineural hearing loss by high-resolution magnetic resonance imaging.

PURPOSE: To determine differences in size of cochlear nerves among subjects with deafness due to connexin 26 (Cx26) mutations, subjects with deafness of unknown origin, and normal hearing subjects by sagittal high-resolution magnetic resonance (HRMR) imaging of the temporal bone. MATERIALS AND METHODS: Cross-sectional and surface areas and volumetric measurements of the cochlear nerve and modiolus were made on HRMR images of the internal auditory canal (IAC) and inner ear in the 3 groups of children (groups 1, 2, and 3). Three-way comparisons of in vivo cochlear nerve measurements on HRMR imaging were made among 17 children with sensorineural hearing loss (SNHL) and no obvious etiology for the hearing loss (group 1), 7 children with profound SNHL due to a Cx26 mutation (group 2), and 10 normal hearing children (group 3). RESULTS: Children with profound SNHL of unknown cause and children with profound SNHL due to a connexin mutation displayed hypoplastic cochlear nerves as compared with normal controls. HRMR imaging of the temporal bone was accurately delineated potential problems with cochlear nerves in 2 of 17 instances where high-resolution computed tomography did not do so. CONCLUSIONS: Accurate and specific measurements of the cochlear nerve and related structures is possible on HRMR imaging of the temporal bone. The size of the cochlear nerve is mildly hypoplastic in children with profound SNHL of unknown causes or children with a deafness-causing Cx26 mutation. HRMR imaging is superior to high-resolution computed tomography in the investigation of profound SNHL in children.

Adolescent↗

Central projections of cochlear nerve fibers in the alligator lizard.

The auditory (cochlear) ganglion cells of the alligator lizard (Gerrhonotus multicarinatus) give rise to two types of peripheral fibers: tectorial fibers, which contact hair cells covered by a tectorial membrane, and free-standing fibers, which contact hair cells without a tectorial membrane. To determine the central projections of these fibers, we applied intracellular and extracellular injections of horseradish peroxidase (HRP) to the peripheral component of the cochlear nerve. After histological processing with diaminobenzidine, individual cochlear nerve fibers could be traced through serial sections with the aid of a light microscope and drawing tube. The projection patterns formed two morphologically distinct groups. Neurons whose peripheral processes contacted tectorial hair cells in the cochlea projected to three divisions of the cochlear nucleus: nucleus magnocellularis lateralis (NML), nucleus magnocellularis medialis (NMM), and nucleus angularis lateralis (NAL). Neurons whose peripheral processes contacted free-standing hair cells projected primarily to the nucleus angularis medialis (NAM), although some also sent a single, thin branch to the NML; these neurons never projected to NAL or NMM. Morphometric comparisons of tectorial and free-standing fibers demonstrate that tectorial fibers have a larger axonal diameter, form a greater number of terminal swellings, and make proportionally more somatic contacts. By correlating the morphologically defined groups with previously reported physiologically defined groups, we conclude that different divisions of the cochlear nucleus are associated with separate frequency ranges and that stimuli in the different frequency ranges may be processed separately in the brain.

Acoustic Stimulation↗

Tonotopic distribution of short-term adaptation properties in the cochlear nerve of normal and acoustically overexposed chicks.

Cochlear nerve adaptation is thought to result, at least partially, from the depletion of neurotransmitter stores in hair cells. Recently, neurotransmitter vesicle pools have been identified in chick tall hair cells that might play a role in adaptation. In order to understand better the relationship between adaptation and neurotransmitter release dynamics, short-term adaptation was characterized by using peristimulus time histograms of single-unit activity in the chick cochlear nerve. The adaptation function resulting from 100-ms pure tone stimuli presented at the characteristic frequency, +20 dB relative to threshold, was well described as a single exponential decay process with an average time constant of 18.6+/-0.8 ms (mean+/-SEM). The number of spikes contributed by the adapting part of the response increased tonotopically for characteristic frequencies up to approximately 0.8 kHz. Comparison of the adaptation data with known physiological and anatomical hair cell properties suggests that depletion of the readily releasable pool is the basis of short-term adaptation in the chick. With this idea in mind, short-term adaptation was used as a proxy for assessing tall hair cell synaptic function following intense acoustic stimulation. After 48 h of exposure to an intense pure tone, the time constant of short-term adaptation was unaltered, whereas the number of spikes in the adapting component was increased at characteristic frequencies at and above the exposure frequency. These data suggest that the rate of readily releasable pool emptying is unaltered, but the neurotransmitter content of the pool is increased, by exposure to intense sound. The results imply that an increase in readily releasable pool size might be a compensatory mechanism ensuring the strength of the hair cell afferent synapse in the face of ongoing acoustic stress.

Acoustic Stimulation↗