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A 48-year-old woman with triple cardiac valve prostheses became completely deaf after bitemporal embolism. The lesions were demonstrated radiologically and neurophysiological investigation confirmed intact peripheral and brainstem pathways. Experimental studies of the auditory pathways are briefly reviewed. Reported cases of cortical deafness are discussed and the rarity of the condition emphasised.
The firing patterns of neurons in central auditory pathways encode specific features of sound stimuli, such as frequency, intensity and localization in space. The generation of the appropriate pattern depends, to a major extent, on the properties of the voltage-dependent potassium channels in these neurons. The mammalian auditory pathways that compute the direction of a sound source are located in the brainstem and include the connection from bushy cells in the anteroventral cochlear nucleus (AVCN) to the principal neurons of the medial nucleus of the trapezoid body (MNTB). To preserve the fidelity of timing of action potentials that is required for sound localization, these neurons express several types of potassium channels, including the Kv3 and Kv1 families of voltage-dependent channels and the Slick and Slack sodium-dependent channels. These channels determine the pattern of action potentials and the amount of neurotransmitter released during repeated stimulation. The amplitude of currents carried by one of these channels, the Kv3.1b channel, is regulated in the short term by protein phosphorylation, and in the long term, by changes in gene expression, such that the intrinsic excitability of the neurons is constantly being regulated by the ambient auditory environment.
In contacting arrays of different types of neurons whose axons have differing targets in the brain stem, the auditory pathway is subdivided into parallel ascending pathways, each of which carries a different type of information. Several distinct arrays of neurons in the ventral cochlear nuclei have anatomical and biophysical specializations which enable them to extract differing facets of acoustic information and to convey it up the auditory pathway. T stellate cells have higher input resistances and have lower firing thresholds than bushy or octopus cells, enabling their firing to be modulated by small currents. Cholinergic currents, driven by neurons in the ventral nucleus of the trapezoid body that are likely to include medial olivocochlear efferents, excite T stellate cells, but have subtle effects on the firing of bushy cells, and have no detectable influence on octopus cells and D stellate cells. We suggest that cholinergic excitation of T stellate cells contributes toward shifting their acoustic dynamic ranges and increasing the encoding of spectral peaks in noisy conditions and in awake animals.
The power spectrum of normal ABR consists of three major parts: low (0-350 Hz: component A), middle (350-700 Hz: component B) and high (700-1200 Hz: component C) frequency components. With digital filtering using fast Fourier transform (FFT), three component waveforms of ABR were obtained and designated as component A, B and C. Component A has a positive peak which corresponds to wave V or the slow component of the original ABR. Component B has three positive peaks (B1-B3) which correspond to wave I, III and V, and component C has five positive peaks (C1-C5) which correspond to wave I-V. These three component waveforms of ABR were analyzed topographically in normal hearing adults and cats. In addition, changes in the topography of three component waveforms of ABR were studied in a series of experimentally induced lesions in the brainstem auditory pathway in cats. The following results were obtained: i) The highest voltage (HV) area of component B1 was detected on the ipsilateral side in normal adults and cats. The HV areas of component C1, C2 and C3 in normal adults and C1, C2 in normal cats were detected on the ipsilateral side. ii) There was a correlation between changes in component C and the lesion site of the auditory pathway. Component C appears to be the most sensitive indicator of the lesion site of the brainstem.
In order to apply the phase spectral analysis of auditory brainstem response (ABR) to the clinical diagnostic test, the phase spectra of ABRs were investigated under adequate stimulus intensity in normal cats and after the destruction of acoustic nerve and brainstem auditory pathways in cats. The results were as follows; i) In normal ABRs, the phase spectra were mainly composed of three frequency components at 0-300 Hz (component A), 300-900 Hz (component B) and 900-1500 Hz (component C). ii) A greater decrease of the component synchrony measure (CSM) occurred if ipsilateral destruction was performed in a peripheral lesion. Lesions of the auditory pathway were followed by a decrease of the CSM of component C in response to contralateral stimulation. These results suggest that the phase spectral analysis of ABRs has significant clinical value in the detection of brainstem lesions.
Brainstem auditory evoked potential (BAEP) changes during intraoperative monitoring may reflect damage to or potentially reversible dysfunction of the ear, the eighth nerve, or the brainstem auditory pathways up to the level of the mesencephalon. They may also be caused by other physiologic mechanisms such as anesthesia, hypothermia, and acoustic masking from drilling noise, or they may result from technical factors that prevent proper stimulus delivery or recording of an evoked potential that is actually present. Cochlear ischemia or infarction resulting from compromise of the internal auditory artery and inner ear damage during temporal bone drilling will affect all BAEP components, including wave I. Direct mechanical or thermal trauma to the eighth nerve will delay, attenuate, and possibly eliminate waves III and V, but wave I, which is generated at the cochlear end of the eighth nerve, may be preserved. During scraping of tumor off the eighth nerve, force applied in an ear-toward-brainstem direction can avulse the fragile fibers of the distal eighth nerve at the area cribrosa. Prolonging the I-to-III interpeak interval during retraction of the cerebellum and brainstem reflects stretching of the eighth nerve, and is often reversible. Vasospasm within the eighth nerve can cause similar, potentially reversible BAEP changes. Damage to the brainstem auditory pathways at or below the level of the mesencephalon will delay and attenuate or eliminate wave V. Wave III is affected similarly if the damage is at or caudal to the region of the superior olivary complex. These BAEP changes may reflect direct mechanical or thermal damage to the brainstem, brainstem compression, or ischemia or infarction resulting from vascular compromise. During BAEP monitoring, examination of the pattern of BAEP changes, analysis of their correlation with surgical maneuvers, and investigation for possible contributory technical factors can help to determine the cause of the BAEP changes and provide the appropriate information to the rest of the surgical team.
Patients with profound binaural sensorineural hearing loss can be treated with cochlear implantation. In recent years, patients who have lost the integrity of the auditory nerve between the spiral ganglion and the cochlear nucleus in the brainstem, and cannot benefit from a cochlear implant, have reported auditory sensations following direct stimulation of the cochlear nucleus with an auditory brainstem prosthesis. To examine the safety and efficacy of such a prosthesis, the cochlear nuclei of guinea-pigs were acutely implanted and stimulated unilaterally with bipolar surface electrodes using the parameters of human implants. The activation of the central auditory pathway by the prosthesis was demonstrated using the 2-deoxyglucose technique. There was broad 2-deoxyglucose labelling in the ipsilateral cochlear nucleus and bilaterally in the inferior colliculi, indicating unusual stimulation of the ipsilateral ascending pathway. Histological examination was performed on all cochlear nuclei. The volumes of cochlear nuclei and the neuron sizes and density in the cochlear nuclei were analysed with three-dimensional reconstruction techniques, and comparisons were made between the stimulated and unstimulated sides. No histological difference, either by direct visual observation or by statistical comparisons, was observed between the stimulated cochlear nuclei and the control sides. These results suggest that in the acute case the auditory brainstem prostheses can safely and effectively activate the auditory pathway in guinea-pigs.
The nucleus sagulum, an area of the midbrain tegmentum, has been considered a component of a lateral tegmental system within the ascending auditory pathway to the thalamus. In this study, connections of the nucleus sagulum within the midbrain were investigated in adult cats. Tracing methods using anterograde and retrograde axonal transport of markers were employed. The nucleus sagulum was identified as a region of principally small neurons (261 +/- 79 micron2) at the margin of the midbrain and neighboring the nuclei of the lateral lemniscus. Injections of tritiated leucine in the nucleus sagulum labeled axons that ended in dense patches within the superficial layers of the caudal portion of the dorsal cortex of the inferior colliculus on the ipsilateral side. Retrograde experiments confirmed this connection. Other axonal projections labeled in the anterograde studies included fibers ending in the dorsomedial nucleus, the superficial layers of the dorsal cortex, and the rostral nucleus of the inferior colliculus with some bilateral distribution. Outside of the inferior colliculus, sagulum injections labeled other axons ending in the ventral intercollicular tegmentum on both sides and in a dorsal and rostral region of the contralateral nucleus sagulum that appeared contiguous with the dorsal nucleus of the lateral lemniscus. The latter region included a population of larger neurons (340-540 micron2) and had different connections with the inferior colliculus. The distribution of axonal labeling after injections in the nucleus sagulum was contrasted with the distribution of projections from several neighboring areas of the lateral tegmentum, including the dorsal nucleus of the lateral lemniscus. None of these areas exhibited connections with the superficial layers of the caudal cortex of the inferior colliculus, which was the major target in the inferior colliculus of the nucleus sagulum. Thus, the results indicated that the nucleus sagulum is distinguished from adjacent regions of the lateral tegmentum by its connectivity. Its association with midbrain auditory pathways is supported by these connections as well as ascending ones to the auditory thalamus.
Auditory brainstem response (ABR) changes in the ischemic brainstem condition and the correlation between ABR and blood flow of the auditory pathway are not clear. In this study, ABR changes in two cases with brainstem ischemia are reported. In order to clarify the correlation between ABR changes and cochlear blood flow, experimental studies on guinea pigs with brain ischemia were performed. Changes of ABR in the human brainstem ischemic condition consisted of a decrease of the amplitudes of all waves and a delay in wave latencies. Even if ABR showed no response, it turned to normal when the blood flow was recovered. In the experimental study, the same changing patterns in ABR occurred in parallel with a decrease of the cochlear blood flow, and the cochlear blood flow was not zero when ABR became non-responsive. This suggests that ABR changes reflect the degree of ischemia in the auditory pathway, and that non-responsive ABR does not imply irreversible ischemic condition.
The auditory pathway of mammals is composed of two complementary ascending afferent and descending efferent independent systems. The brainstem nuclei and cochlear projections for these systems are now well-known. In addition, a highly conspicuous distribution for serotonergic fibers was recently reported. This study focused on these serotonergic fibers and their neurons of origin. We identified several different types of serotonergic brainstem neurons surrounding the superior olivary complex and around the periolivary nuclei. Even though the 5-hydroxytryptamine (5-HT) efferent cochlear innervation originates in the periolivary area of the superior olivary complex system projecting to the cochlea, it is not involved in the transduction of pure tones during auditory processing. However, recent findings, after cochlear blockade of serotonin transporters, strongly suggested that this neuroactive substance has an important turnover within the auditory receptor. The presence of a conspicuous peripheral nerve distribution together with a particular brainstem origin could define a complex role for this innervation. Therefore, 5-HT fibers projecting to the cochlea might be involved, as in other parts of the auditory pathway, in alertness, attention, control of sleep or wakefulness cycles, and state of urgency prior to the transduction processing at the auditory receptor. A lack, or reduction, of the function of these fibers could result in pathological alterations.
Before mice start to hear at approximately postnatal day 10, their cochlear inner hair cells (IHCs) spontaneously generate Ca(2+) action potentials. Therefore, immature IHCs could stimulate the auditory pathway, provided that they were already competent for transmitter release. Here, we combined patch-clamp capacitance measurements and fluorimetric [Ca(2+)](i) recordings to study the presynaptic function of IHCs during cochlear maturation. Ca(2+)-dependent exocytosis and subsequent endocytic membrane retrieval were already observed near the date of birth. Ca(2+) action potentials triggered exocytosis in immature IHCs, which probably activates the auditory pathway before it becomes responsive to sound. IHCs underwent profound changes in Ca(2+)-channel expression and secretion during their postnatal development. Ca(2+)-channel expression increased toward the end of the first week, providing for large secretory responses during this period and thereafter declined to reach mature levels. The efficacy whereby Ca(2+) influx triggers exocytosis increased toward maturation, such that vesicle fusion caused by a given Ca(2+) current occurred faster in mature IHCs. The observed changes in Ca(2+)-channel expression and synaptic efficacy probably reflected the ongoing synaptogenesis in IHCs that had been described previously in morphological studies.
An investigation is underway in deaf white cats in order to clear up some problems about the timing of cochlear degeneration, the relationships between physiological and histological findings, and the consequential state of central auditory pathways. The first results reported here show that degeneration of sensory structures was much more advanced than physiological results lead us to believe. The possibility of direct fibre stimulation is discussed. Although degeneration of nervous structures was delayed compared with sensory ones, some early abnormalities in myelination were found. In the adult, completely deaf for years, the electrical stimulation of cochlear nuclei evoked normal-looking field responses at the cortical level. Thus some degree of auditory pathway functional integrity appeared even long after they were disconnected from receptors.
The neural generators of the brainstem auditory evoked potentials (BAEPs) in humans are not completely known. Attempts to identify the anatomical location of the neural generators of the human BAEP based on the results of studies in animals commonly used in auditory experimentation have been difficult because of the considerable anatomical differences between the ascending auditory pathways in humans and animals. The authors of this study compared recordings obtained from different locations on the lateral side of the brainstem in six patients undergoing microvascular decompression surgery for a cranial nerve disorder affecting the fifth cranial nerve (i.e., trigeminal neuralgia). Ipsilateral click stimulation evoked prominent responses from the caudal aspect of the pons up to the junction between the pons and the midbrain, but all components of the responses with latencies shorter than 8 msec had smaller amplitudes when recorded at more rostral locations. Components with latencies in the range of peak V elicited by contralateral click stimulation had their largest amplitudes when recorded from the lateral brainstem at the level of the fourth cranial nerve (thus, close to the inferior colliculus). Earlier components of the contralateral responses (latencies in the range of the latency of peak III) had their largest amplitudes when recorded from the caudal lateral brainstem. The results of this study indicate that the part of the uncrossed auditory pathway that is located rostral to the cochlear nucleus contributes little to the farfield potentials (i.e., BAEP), and it is doubtful whether the contralateral response that can be recorded at the level of the cochlear nucleus contributes noticeably to the BAEP.
Impact of early post-natal deafening on auditory pathways was investigated in newborn rats deafened by daily amikacin injections from P7 to P16 inducing a complete destruction of the organ of Corti. The expression of mRNAs encoding N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) and gamma-aminobutyric acid type A (GABA(A)) receptor subunits was then studied by in situ hybridization in the dorsal and ventral cochlear nucleus and in the central nucleus of the inferior colliculus (CNIC). Early post-natal deafening decreased bilaterally the expression of mRNAs encoding NR1, NR2a, NR2b and flop isoforms of AMPA receptors. On the contrary, it increased the expression of mRNAs encoding some GABA(A) subunits (alpha1, beta1, gamma2) and flip isoforms of AMPA receptors. These changes were more pronounced in cochlear nuclei than in CNIC. They suggest that auditory sensation is essential in the normal development of central auditory pathways.
The influence of age at the time of implantation of a stimulating electrode unilaterally in the inner ear on central auditory pathways was investigated in rats deafened shortly after birth. Immunoreactivity for Fos served as a functional marker of neuronal activity. Electrodes were implanted in the left cochlea of rats aged 3 weeks or 4 months. Stimulation lasted 45 minutes, then rats were sacrificed and tissues processed for immunocytochemistry. The younger animals showed significantly more neurons with Fos immunoreactivity bilaterally in the dorsal cochlear nuclei (DCN) and inferior colliculi (IC) than the older rats or control animals with normal hearing receiving the same stimulation. Activity was more prominent in the left DCN and right IC. The results show that electrical stimulation of the inner ear is more effective in younger animals in eliciting gene expression associated with development of a functional network in the auditory pathways. This suggests that deaf children should be provided with cochlear implants as early as possible.
Venom sac extract from the hornet Vespa orientalis was injected (via the subclavian artery) into cats and its effects on evoked potentials in two different sensory pathways (auditory and somatosensory) was investigated. A comparison was made between the venom sac extract from adult hornets and that from young (0-24 hr of age) hornets. There was a bimodal change in blood pressure, a hypothermic effect and a decrease in amplitude of the last waves of the auditory and somato sensory pathways when venom sac extract of adult hornets was injected. Venom sac extract from young hornet workers had the same influence on the blood pressure, did not affect thermoregulation and the effect on the auditory and somato sensory pathways were less consistent. Adult venom sac extract had mainly a central effect whilst the venom sac extract from young hornets (in larger doses) affected the central and/or peripheral nervous system. The central effects could be interpreted as due to opening of the blood-brain barrier by the venom.
We investigated the effects of intracochlear electrical stimulation (ICES) on auditory pathways of neonatal rat deafened by daily amikacin injections. Expression of mRNAs encoding ionotropic glutamate receptor subunits such as alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) and N-methyl-D-aspartate (NMDA), and gamma-aminobutyric acid type A (GABA(A)) receptor subunits was assessed by in situ hybridization in the dorsal (DCN) and the ventral cochlear nucleus (VCN) and in the central nucleus of the inferior colliculus (CNIC). After 15 days of daily unilateral ICES, the expressions of NR1, NR2b and NR2c subunits of NMDA receptor, that of GluRA, B, C, D flop isoforms of AMPA receptor and that of some GABA(A) subunits (alpha1, beta1, gamma1, gamma2) were increased bilaterally in the DCN, VCN and the CNIC. These changes last over a week after stimulation for only NR1 and NR2c. These modifications might be related to long lasting synaptic plasticity of brainstem auditory pathways. As far as analogy to deaf children can be made, early electrical stimulation might be of interest to maintain neuronal networks.
AIMS: Whereas cortical EEG effects of benzodiazepines are well characterized, information about benzodiazepine effects in other areas of the central nervous system is sparse. This study investigated the action of midazolam and its active metabolite alpha-hydroxy-midazolam on different parts of the auditory pathway in six healthy volunteers in a randomized, double-blind, three-way cross-over study. METHODS: Acoustically evoked short (SLP) and middle (MLP) latency potentials, transitory evoked otoacoustic emissions (TEOAE), and EEG power spectra were analysed after short i. v. injections of placebo, or 0.15 mg kg-1 midazolam, or alpha-hydroxy-midazolam, respectively. RESULTS: All subjects fell asleep during the 4 min infusion of active drug. SLP showed a significant transient increase of Jewett wave V 10 min after injection for midazolam and alpha-hydroxy-midazolam while the latency of wave I was unchanged. Both benzodiazepines induced a marked and long-lasting MLP amplitude decrease for 240 min with slow recovery over the following 360 min. No changes of TEOAE were observed. In agreement with earlier reports, increases in EEG beta activity and decreases in alpha activity were observed after administration of either drug. CONCLUSIONS: Systemically administered benzodiazepines modulate the auditory pathway above the level of the cochlea. While SLP changes were closely associated with sedation and high plasma benzodiazepine concentrations, MLP effects persisted for hours after sedation even at low benzodiazepine plasma levels. Evoked potentials may therefore be more sensitive than EEG as a tool to monitor benzodiazepine effects.