Postnatal development of auditory nerve and cochlear nucleus neuronal responses in kittens

Neurons located within the auditory periphery of kittens (i.e., primary auditory nerve fibers and neurons of the cochlear nucleus (CN) exhibit similar response properties throughout the early stages of postnatal development. Neural thresholds to acoustic stimuli are uniformly high, spontaneous and acoustically-evoked discharge rates are low, input/output slopes are shallow, and temporal discharge patterns are markedly immature. Phase-locking abilities are poor in developing mammals and all neurons exhibit broad bandpass tuning curves, with center frequencies clustering near 1.5 kHz. Throughout the first week, response thresholds, maximum discharge rates, rate-intensity slopes, dynamic ranges and other response indices remain essentially unchanged. Thereafter, between the 7th and 20th postnatal days, peripheral auditory development proceeds rapidly, such that thresholds, tuning properties, temporal discharge patterns, and input/output functions achieve maturity. The role of synaptogenesis in the development of adult response properties has been studied through microionophoresis of neuroactive molecules onto the surface of neurons in the caudal divisions of the cochlear nuclei of developing kittens. Results of preliminary experiments suggest that inhibitory postsynaptic receptor function precedes intrinsic excitatory neurotransmission. Furthermore, during the first two weeks of postnatal development in kittens, GABA microionophoresis onto immature caudal CN neurons, exhibiting sustained responses to acoustic stimuli, converts response patterns to the onset type in the majority of neurons encountered.     

Electrical stimulation of the auditory nerve: effects of pulse width on frequency discrimination.

Effects of pulse width on discrimination of simultaneous changes in frequency and level of electrical pulse trains were studied in a monkey subject with a cochlear implant. At test-stimulus levels where performance was minimum, frequency difference limens were larger for longer-duration pulses than that for shorter-duration pulses. Several factors may have contributed to these differences.     

Electrical stimulation of the cochlear nerve in deafness mice

The deafness mouse mutant provides a useful animal model for studying the central consequences of complete auditory deprivation during development. The object of this study was to record inferior colliculus-evoked potentials in mutant and control mice, using short electrical pulses to stimulate either the whole cochlea or the cochlear nerve directly. In both experiments, evoked potentials were readily recorded in the mutant and control mice, indicating that some central connections are functional, even though the auditory pathway has received no stimulus-related input throughout development. The results are relevant to the clinical problem of restoring auditory function in the profoundly deaf using peripheral electrical stimulation.     

Internal auditory canal morphology in children with cochlear nerve deficiency.

OBJECTIVE: To describe the internal auditory canal (IAC) and inner ear morphologic characteristics of children with cochlear nerve (CN) deficiency. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Fourteen children with small or absent (deficient) CNs have been identified by means of high-resolution magnetic resonance imaging (MRI). INTERVENTIONS: MRI of the brain. Clinical evaluation. MAIN OUTCOME MEASURES: Review of medical records, audiological testing results, and imaging studies. Images were evaluated for the structure of the cochlear, vestibular and facial nerves, IACs and inner ears. Audiometric thresholds were evaluated in all subjects. METHODS: Fourteen children with small or absent (deficient) CNs have been identified by means of high-resolution MRI. A review of the medical records, audiologic testing results, and imaging studies was undertaken. The images were evaluated for the structure of the cochlear, vestibular and facial nerves, IACs, and inner ears. The audiometric thresholds were evaluated in all subjects. RESULTS: Among the 14 patients, 5 had known syndromes. MRI allowed an exact specification of the nervous structures within all ears with normal-size IACs. Precise characterization of the nerves in ears with small IACs was more difficult, requiring a consideration of both imaging findings and functional parameters. Five children had bilateral deficient CNs, whereas the remaining 9 subjects were affected unilaterally. Thus, 19 ears had CN deficiency (absent CN, 16; small CN, 3). Eleven ears had normal-size IACs and deficient CNs. Of the 9 ears with small IACs, 8 had deficient CNs (absent, 7; small, 1) on the basis of both MRI and functional assessments. Two ears with small IACs had clear morphologic and/or functional evidence for the presence of a CN: one had a small-size CN on MRI, whereas another had a single nerve in a small IAC with present facial and auditory functions. CONCLUSION: The findings of this study suggest that CN deficiency is not an uncommon cause of congenital hearing loss. The findings that most ears with CN deficiency had normal IAC morphology and that two ears with small IACs had CNs present indicate that IAC morphology is an unreliable surrogate marker of CN integrity. On the basis of these findings, we think that high-resolution MRI, rather than CT imaging, should be performed in all cases of pediatric hearing loss, especially in those cases where profound hearing loss has been documented. For ears with small IACs, the resolution of MRI currently remains limiting. In these cases, the determination of CN status frequently requires a variety of anatomic (CT and MRI) and functional tests (auditory brainstem response, otoacoustic emissions, behavioral audiometry, and physical examination).     

Cochlear pathology following chronic electrical stimulation of the auditory nerve. I: Normal hearing kittens.

The present study examines the histopathological effects of long-term intracochlear electrical stimulation in young normal hearing animals. Eight-week old kittens were implanted with scala tympani electrode arrays and stimulated for periods of up to 1500 h using charge balanced biphasic current pulses at charge densities in the range 21-52 microC cm-2 geom. per phase. Both click and electrically evoked auditory brainstem responses were periodically recorded to monitor the status of the hair cell and spiral ganglion cell populations. In addition, the impedance of the stimulating electrodes was measured daily to monitor their electrical characteristics during chronic implantation. Histopathological examination of the cochleas showed no evidence of stimulus induced damage to cochlear structures when compared with implanted, unstimulated control cochleas. Indeed, there was no statistically significant difference in the ganglion cell density adjacent to the stimulating electrodes when compared with a similar population in implanted control cochleas. In addition, hair cell loss, which was restricted to regions adjacent to the electrode array, was not influenced by the degree of electrical stimulation. These histopathological findings were consistent with the evoked potential recordings. Finally, electrode impedance data correlated well with the degree of tissue growth observed within the scala tympani. The present findings indicate that the young mammalian cochlea is no more susceptible to cochlear pathology following chronic implantation and electrical stimulation than is the adult.     

Diameter of the cochlear nerve in deaf humans: implications for cochlear implantation.

Although the parameters that are most important for postoperative speech perception in cochlear implantation have not been identified, it is assumed that the numbers of remaining cochlear neurons and spiral ganglion cells in the implanted deaf ears are critical. In this study, we evaluated the correlation of the maximum diameter of the cochlear and vestibular nerve trunks with the number of spiral ganglion cells in horizontal sections of the temporal bone of 42 patients who were profoundly deaf during life, and in 5 patients with normal hearing. The maximum diameters of the cochlear, vestibular, and eighth cranial nerves were significantly smaller in the deaf population as compared to normal-hearing controls. In addition, the counts of the remaining spiral ganglion cells were significantly correlated with the maximum diameter of the cochlear (p = .0006), vestibular (p = .001), and eighth cranial nerves (p = .0003). The regression equation estimated that 25% of the variance of the spiral ganglion cell count was predicted by the maximum diameter of the eighth nerve. Although the results of this study suggest that preoperative radiographic imaging of the diameter of the eighth nerve may be helpful in predicting the residual spiral ganglion cell count, the wide variability of diameters of the eighth nerve in hearing and deaf subjects militates against this theoretic usefulness.     

Electrical stimulation rate effects on speech perception in cochlear implants

The objective of this study was to explore cochlear implant users’ speech perception performance in quiet and in noise for low to moderate stimulation rates. Eight postlingually deaf adult users of the Nucleus CI24 cochlear implant (contour electrode array) using the ESPrit 3G speech processor participated in this study. Monosyllabic word recognition in quiet and sentence perception in noise was evaluated for low to moderate stimulation rates of 275, 350, 500, and 900 pulses-per-second/channel (pps/ch). All four stimulation rate programs were balanced for loudness. A repeated ABCD experimental design was employed. Take home practice was provided with each stimulation rate. Subjects also responded to a comparative questionnaire to examine their rate preference for a variety of listening situations. Results for six of the eight subjects showed no significant effect of rate for monosyllables in quiet. However, results for the sentence test in noise demonstrated improvements with 500 or 900 pps/ch stimulation rates in seven out of the eight subjects. Although there was not a close relationship between each subject's subjective preference and the rate program that provided best speech perception, most subjects indicated a preference for 500 pps/ch rate in noise.     

Assessing auditory nerve condition by tone decay in deaf subjects with a cochlear implant

Abstract

The condition of the auditory nerve is a factor determining hearing performance of cochlear implant (CI) recipients. Abnormal loudness adaptation is associated with poor auditory nerve survival. We examined which stimulus conditions are suitable for tone decay measurements to differentiate between CI recipients with respect to their speech perception. Tone decay was defined here as occurring when the percept disappears before the stimulus stops. We measured the duration of the percept of a 60-s pulse train. Current levels ranged from below threshold up to maximum acceptable loudness, pulse rates from 250 to 5000 pulses/s, and duty cycles (percentages of time the burst of pulses is on) from 10% to 100%. Ten adult CI recipients were included: seven with good and three with poor speech perception. Largest differences among the subjects were found at 5000 pulses/s and 100% duty cycle. The well performing subjects had a continuous percept of the 60-s stimulus within 3?dB above threshold. Two poorly performing subjects showed abnormal loudness adaptation, that is, no continuous percept even at levels greater than 6?dB above threshold. We conclude that abnormal loudness adaptation can be detected via an electric tone decay test using a high pulse rate and 100% duty cycle.     

The effects of auditory deprivation on morphological maturation of the ventral cochlear nucleus

Summary The volumes of the auditory brainstem nuclei and age-related auditory brainstem response (ABR) thresholds were analyzed in homozygote (je/je) and heterozygote (je/+) jerker mutant mice. Altogether 97 mice were used in the study. Je/je mice never develop any hearing. The dorsal (DCN) and ventral (VCN) cochlear nuclei were found to have stopped their growth at 56 days after birth. In je/+ mutants, ABR thresholds remained normal or nearnormal for 3–6 months, whereas VCN and DCN volumes remained unchanged at least after 56 days after birth. There is no significant difference in DCN volume in je/je and je/+ mice. However, the VCN volume and the cross-sectional area of globular cells were both significantly larger in je/+ than in je/je mice (P<0.01). These findings show that auditory deprivation during the maturation of hearing in je/je mutants causes an incomplete maturation of only the ventral cochlear nucleus.Supported by grants from the Swedish Medical Research Council (12X-7305), the National Institutes of Health (NS-19238), the Foundation Tysta Skolan (MA), the Ragnar and Torsten Söderberg Foundation (MA) and the University of Umeå     

The effects of auditory deprivation on morphological maturation of the ventral cochlear nucleus

The volumes of the auditory brainstem nuclei and age-related auditory brainstem response (ABR) thresholds were analyzed in homozygote (je/je) and heterozygote (je/+) jerker mutant mice. Altogether 97 mice were used in the study. Je/je mice never develop any hearing. The dorsal (DCN) and ventral (VCN) cochlear nuclei were found to have stopped their growth at 56 days after birth. In je/+ mutants, ABR thresholds remained normal or near-normal for 3-6 months, whereas VCN and DCN volumes remained unchanged at least after 56 days after birth. There is no significant difference in DCN volume in je/je and je/+ mice. However, the VCN volume and the cross-sectional area of globular cells were both significantly larger in je/+ than in je/je mice (P less than 0.01). These findings show that auditory deprivation during the maturation of hearing in je/je mutants causes an incomplete maturation of only the ventral cochlear nucleus.     

Electrical stimulation of cochlear efferents at the round window reduces auditory desensitization in guinea pigs. I. Dependence on electrical stimulation parameters

Electrical stimulation at the round window with pulsed short trains has been shown to elicit classical efferent effects on N1 amplitudes at the cochlea. This report demonstrates that round window stimulation as a continuous burst can reduce temporary threshold shifts (TTS) caused by a simultaneous monaural loud sound exposure. This result is similar to recent reports that stimulation of the crossed olivocochlear bundle (COCB) at the floor of the fourth ventricle can reduce TTS. Like COCB stimulation at the brainstem, the effect of round window stimulation could be abolished by strychnine, with a time course paralleling the blocking action of strychnine on the traditional COCB effects of pulsed short trains on N1 amplitudes. This report also established parameters for optimal effects of the round window stimulus and found them to be similar to the optimal parameters for the effects of brainstem stimulation on TTS. Tonic effects on TTS were also observed, with reductions in TTS being obtained as much as 7 min after a 1 min-long round window stimulus. Such tonic effects did not appear to be due to persistent effects at the cochlea but were suggested to be due to a long term resetting of some central site activated by antidromic stimulation from the round window.     

Neuronal morphology in the human cochlear nucleus

Neuronal morphology in the human cochlear nucleus was studied with a Golgi method to better understand the organization of the nucleus. In ventral portions of the nucleus, three principal cell types and two small cell types previously seen in animals were found. In the dorsal portions of the nucleus, predominant cell types found in animals appear to be absent, indicating that cellular organization here is quite different from that in animals. On the other hand, cell morphology in the ventral nucleus suggests that signal processing here is fundamentally similar to that in animals. A review of the organization of these cells in animals is presented to provide a context of present results. The findings have great relevance in light of efforts to implant electrical prostheses in the nucleus.     

Electrical stimulation of the auditory nerve: II. Effect of stimulus waveshape on single fibre response properties

To investigate the generation of action potentials by electrical stimulation we studied the response of auditory nerve fibres (ANFs) to a variety of stimulus waveforms. Current pulses were presented to longitudinal bipolar scala tympani electrodes implanted in normal and deafened cochleae. Capacitively coupled monophasic current pulses evoked single ANF responses that were more sensitive to one phase (the ‘excitatory’ phase) than the other. Anodic pulses produced a significantly shorter mean latency compared with cathodic pulses, indicating that their site for spike initiation is located more centrally along the ANF. The fine temporal structure of ANF responses to biphasic pulses appeared similar to that evoked by monophasic pulses. An excitatory monophasic pulse evoked a significantly lower threshold than a biphasic current pulse having the same polarity and duration leading phase, i.e. the addition of a second phase leads to an increase in threshold. Increasing the temporal separation of the two phases of a biphasic pulse resulted in a moderate reduction in threshold which approached that of an excitatory monophasic pulse for interphase gaps >100 μs. Greater threshold reductions were observed with narrower current pulses. There was a systematic reduction in threshold with increasing pulse width for biphasic current pulses, reflecting the general charge-dependent properties of ANFs for narrow pulse widths. Chopped biphasic current pulses, which uniformly delivered multiple packets of charge (2×30 μs, 3×20 μs or 6×10 μs) with the same polarity over a 120 μs period, followed by a similar series in the reverse polarity, demonstrated the ability of the neural membrane to integrate sub-threshold packets of charge to achieve depolarisation. Moreover, thresholds for these current pulses were 1.5 dB lower than 60 μs/phase biphasic current pulses with no interphase gap. Finally, stimulation using charge-balanced triphasic and asymmetric current pulses produced systematic changes in threshold and latency consistent with the charge-dependent properties of ANFs. These findings provide insight into the mechanisms underlying the generation of action potentials using electrical stimuli. Moreover, a number of these novel stimuli may have potential clinical application.     

Effects of stimulation by cochlear implant on the cochlear nerve

Degeneration of the cochlear nerve before and after placement of the cochlear implant might influence the efficacy of the device. We examined histological characteristics, including the caliber of the cochlear nerve fibers of the central segment proximal to the porus acusticus, in three profoundly deaf patients. Two of them used a cochlear implant for many years longer in one ear than in the other, and one used an implant in one ear only. No qualitative or quantitative differences between the two sides were found. However, in all three cases we found that the cochlear nerves on both sides were substantially degenerated. These results indicated no noticeable effects of stimulation by the cochlear implant on the central portion of the cochlear nerve.     

Plastic changes in the auditory cortex of congenitally deaf cats following cochlear implantation.

Congenitally deaf cats were used as a model for human inborn deafness and auditory deprivation. The deaf cats were supplied with a cochlear implant, chronically exposed to an acoustic environment and conditioned to acoustic stimuli. In case of early implantation the cats learned to make use of the newly gained auditory channel behaviourally. Neurophysiological and fMRI data showed that the central auditory system was recruited, if implantation took place within a sensitive period of <6 months.     

Phoneme recognition by deaf individuals using the multichannel nucleus cochlear implant.

Experiments have been carried out to determine which cues are used in phoneme identification by deaf individuals using a cochlear implant. Five deaf individuals with a Nucleus 22-channel cochlear implant were tested with open set speech audiometry in free field without lipreading. Speech material consisted of lists of Dutch words of the Consonant-Vowel-Consonant type (CVC-words). Word scores ranged from 0 to 22%, phoneme scores from 11 to 54%. For each subject the responses to the initial consonant, the vowel and the final consonant were entered into separate confusion matrices. Kruskal analysis, which provided a geometric representation of these confusions, showed that in the recognition of consonants the feature of voicing is all important. Vowels were identified on the basis of the frequencies of the first and second formants. In one subject the electrode array could only partially be inserted into the cochlea, leaving roughly half the second formant area of the electrode array outside the cochlea. For this subject vowel identification was based upon the first formant and vowel duration; there was no contribution of second formant information to vowel identification. Compressing the first and second formant frequency to the limited intracochlear array did not enhance transmission of second formant information and did not improve performance. The basic findings for consonant and vowel recognition could be explained by the speech coding strategy of the Nucleus speech processor in which voicing determines stimulus periodicity and formant frequencies determine channel selection. Kruskal analysis of phoneme confusions may aid in programming and evaluating the performance of the Nucleus cochlear implant.     

Feasibility of multichannel human cochlear nucleus stimulation.

Bipolar electrical stimulation of the brainstem cochlear nucleus (CN) following acoustic tumor removal in an only-hearing ear can provide beneficial hearing. However, the benefits of multichannel stimulation have yet to be defined. Following removal of a second acoustic tumor in a patient with neurofibromatosis 2, a Nucleus mini-22 channel implant device was inserted with the electrode array tip from the foramen of Luschka cephalad along the root entry zone of the eighth nerve, secured by a single suture superficially in the brain stem. Initial stimulation on the sixth postoperative day indicated that electrodes 18 to 22 were capable of CN stimulation without seventh nerve stimulation. Presumed electrode migration precluded further CN stimulation 1 month later. This report illustrates the feasibility of brainstem CN stimulation with an existing multichannel system.