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PubMed1982

Tonotopic organization in the central auditory pathway of the Mongolian gerbil: a 2-deoxyglucose study.

The uptake of 2-deoxyglucose (2-DG) was employed to map functional activation of the central auditory pathway in the mongolian gerbil, during 85 dB SPL stimulation with pure tonal stimuli at frequencies of 0.75, 3.0, or 12.0 kHz. Pure tones produced foci of very high 2-DG uptake, when compared to adjacent tissue, in the cochlear nucleus, superior olivary complex, and inferior colliculus. Less distinct areas of elevated 2-DG uptake were seen in the dorsal and ventral nuclei of the lateral lemniscus, medial geniculate nucleus, and auditory cortex. Little or no change in the distribution of 2-DG uptake was noted in the nucleus of the trapezoid body. The location of discrete regions of relatively high 2-DG uptake varied systematically with stimulus frequency. The tonotopic organization demonstrated by 2-DG mapping agreed well with the results of previous electrophysiological studies for most structures. However, in the inferior colliculus, stimulus-evoked increases in 2-DG uptake were found to occur in a fixed pattern of three to four bands across the central nucleus, which did not correspond to any previously reported anatomical or physiological organization. Pure tonal stimuli activated discrete portions of this banding pattern. Also, a small area at the ventromedial edge of the colliculus was more broadly tuned than other regions of the nucleus. It is concluded that 2-DG uptake is well suited to the investigation of tonotopic organization. This technique reveals patterns of activation which have not been observed with other methodologies.

Animals↗
PubMed1999

Transient CD15 expression reflects stages of differentiation and maturation in the human subcortical central auditory pathway.

The expression of the terminal saccharide determinant CD15 (3[a1-3]-fucosyl-N-acetyl-lactosamine) was evaluated in the central auditory system of the human developing brain by using monoclonal antibodies against this epitope. CD15 immunoreactivity was first observed in the ventral cochlear nucleus at 10 weeks of gestation, whereas the dorsal cochlear nucleus became positive from 13 weeks of gestation. In both nuclei, the intensity of immunoreactivity increased until 16 weeks of gestation and lasted until 25 weeks of gestation. In the inferior colliculi, CD15 was poorly expressed in the central nucleus from 13 to 23 weeks of gestation and later with moderate levels until birth. Within the medial geniculate nucleus, a biphasic pattern of expression was observed with peaks around 14-17 and 21-24 weeks of gestation. Heterogeneous expression in the medial geniculate nucleus, which was associated either with neurons or the neuropil, allowed distinction of subnuclei. In many of the auditory pathway structures (e.g., ventral cochlear nucleus and central nucleus of the inferior colliculus), a heterogeneous pattern of CD15 expression in the form of repeating parallel bands, possibly related to tonotopic organization, became transiently apparent around 23 weeks of gestation, whereas in the magnocellular part of the medial geniculate nucleus, a striking modular or compartmental arrangement of immunoreactive structures (which could also be associated with tonotopic organization) was also noted at about 23 weeks of gestation. We propose that the initiation of CD15 expression in each nucleus heralds the appearance of functional contacts and that high levels of neuropil labeling are related to the formation of nonstabilized synaptic contacts. Thus, transient CD15 expression in the central auditory system is possibly correlated with phases of functional plasticity in this pathway.

Aging↗
PubMed2001

Regeneration and recovery of the hearing function of the central auditory pathway by transplants of embryonic brain tissue in adult rats.

The present study is the first report of successful regeneration and recovery of hearing function of the central auditory pathway after transection in the adult rat. The ventral cochlear tract in the brain stem to pons was transected on one side in adult rats. Tissue from embryos (E14 to E16) was used to cover the lesion site. In 30% of the rats examined, the axons regrew beyond the transected site and regenerated into the denervated side and terminated at the normal targets. The hearing function of rats was elucidated by recording the auditory brain stem response (ABR). Rats with successful regeneration showed nearly normal ABR. In rats receiving simple transection without covering embryonic tissue, there was no regeneration and hearing function did not recover. Thus, the present findings contradict the widely held view that the adult mammalian central auditory system cannot be restored following damage.

Animals↗
PubMed2005

Functional studies of the human auditory pathway after monaural stimulation with pure tones. Establishing a normal database.

CONCLUSIONS: Bilateral activation of Brodmann area 39 provides functional support for the concept of bilateral cortical activation with auditory stimulation. The observation that when Brodmann area 39 is activated, area 38 of the temporal lobe is simultaneously inhibited (a functional observation that has seemingly not been previously reported) supports the concept that inhibitory as well as excitatory relays play a role in the auditory pathways. In addition, this report helps to establish a functional database for future studies. OBJECTIVES: (i) To determine which areas of the cerebral cortex and basal ganglia are activated when the left and right ears are monaurally stimulated with pure tones, and what type of response (e.g. excitatory or inhibitory) occurs in these different areas. (ii) To determine the degree of ipsi- and/or contralateral cortical activation and/ or inhibition depending on the ear that is stimulated. (iii) To use this information as an initial step to develop a normal functional database for future studies. MATERIAL AND METHODS: A brain perfusion single-photon emission CT (SPECT) evaluation was conducted using auditory monaural stimulation with pure tones in 10 normal volunteers. Both ears were tested independently (20 examinations in total). 99mTc hexamethyl-propylenamine-oxime was injected while pure tones were delivered, and the SPECT imaging was done 1 h later. RESULTS: After delivering pure tones there was bilateral cortical activation in Brodmann areas 39 and 40, regardless of which ear was stimulated. Despite marked hyperperfusion in both areas 39, a more intense response was seen on the left compared to the right side, although this was not statistically significant. There was also activation in the executive frontal cortex areas 9 and 10 as well as in the temporal Brodmann areas 21 and 22. Simultaneously, area 38 of the temporal lobe was deactivated. In the subcortical structures there was also marked activation in both thalami and deactivation of the caudate nuclei without lateralization.

Acoustic Stimulation↗
PubMed1984

Anatomy of the auditory pathways, with emphasis on the brain stem.

The principal auditory leading to the cerebral cortex and therewith to conscious perception passes from the cochlea, via the cochlear nuclei, the inferior colliculus and the medial geniculate body to the contralateral auditory cortex in the temporal lobe. All components of this pathway are cochleotopically organized. The fibre stream leading from the cochlear nuclei to the contralateral inferior colliculus consists of both direct and multisynaptic components. The latter are interrupted one or more times in the superior olivary complex and/or the nuclei of the lateral lemniscus, cell assemblies that lie embedded into the main ascending fibre stream. The auditory cortex receives not only impulses from the contralateral cochlea, but also from the ipsilateral cochlea. The ipsilateral projection reaches the ipsilateral inferior colliculus after a synaptic interruption in the ipsilateral superior olivary complex. Fibres conveying impulses from the contralateral side back to the ipsilateral side are probably also involved. The auditory system of the brain stem is characterized by the presence of several well-developed commissures. Most of these contain, in addition to decussating components, true commissural fibres. The various auditory centres in the brain stem are not only way stations in the ascending auditory pathways, but also serve as relays in descending auditory projections. Most important among the latter is the cortico-cochlear projection which is synaptically interrupted in the inferior colliculus and the periolivary nuclei. The final link in this descending projection is formed by the bundle of Rasmussen, the fibres of which leave the central nervous system and innervate the inner and outer hair cells in the organ of Corti. The pathways for the auditory startle response, the auditory orientation reflex and the stapedius and tensor tympani reflexes are briefly described.

Auditory Pathways↗
PubMed1995

Abrupt unilateral deafness modifies function of human auditory pathways.

We studied nine patients with unilateral abrupt deafness caused by acoustic neuroma surgery. Cortical responses to tones delivered to the intact ear were recorded postoperatively with a 122-channel whole-scalp neuromagnetometer. In three patients, followed for 12 months with 2-4 measurements, evoked responses originating in the auditory cortices were weak and delayed one month after the operation in both hemispheres. During the follow-up, the amplitudes reached the control level. No response abnormalities were found in patients who were studied 1.5-4.5 years after the operation. Our findings suggest that abrupt unilateral deafness causes immediate changes in the function of auditory pathways of adult humans and that reorganization takes place within 1 year.

Adolescent↗
PubMedDate not supplied

Auditory pathway encoding and neural plasticity in children with learning problems.

An inability to process auditory information, especially speech, characterizes many children with learning and attention problems. Our working hypothesis is that these speech-sound perception problems arise, at least in some cases, from faulty representation of the speech signal in central auditory centers. Preconscious neurophysiologic representation of sound structure by central auditory pathway neurons can be reflected by subcortical and cortical aggregate neural responses. These neurophysiologic responses can be modified by perceptual learning. Our research has shown that some children with learning problems demonstrate abnormal perception and neural representation of certain speech sounds. Differences between normal and learning-impaired groups can be attributable to aspects of neural synchrony that are reflected in aggregate neural responses. Deficiencies in neural synchrony in these children are apparent in subcortical (as well as cortical) representations of speech-sound structure, and these timing deficits are related to performance on speech-sound perception and learning measures. Moreover, impaired perception and neurophysiologic encoding of speech sounds can be improved with cue enhancement and can be modified by perceptual learning associated with auditory training.

Child↗
PubMed1996

Hearing loss in multiple sclerosis: localization of the auditory pathway lesion according to electrocochleographic findings.

Multiple sclerosis is known to affect the myelin of the auditory pathway resulting in acute hearing loss. Two cases of sudden deafness due to multiple sclerosis have been evaluated by conventional audiometry, brainstem auditory evoked response audiometry and transtympanic electrocochleography. The abnormalities of the compound action potential in both patients (enhanced latency, abnormal adaptation using fast stimulus rate) and the normal receptor potentials (cochlear microphonic, summating potential), as well as the absence of brainstem responses suggest a disturbance of synchronization at the level of the first auditory neurone. The electrocochleography provides valuable information for the topodiagnosis of this and other neural hearing losses, especially in the absence of reliable brainstem responses.

Adult↗
PubMed1999

The effect of 1,3-dinitrobenzene on the functioning of the auditory pathway in the rat.

1,3-Dinitrobenzene (DNB) has previously been shown to be neuropathic, causing gliovascular lesioning in the rat brainstem, with the nuclei of the auditory pathway being particularly affected. Lesion severity was shown to be dependent on functional activity, which could be markedly decreased within one pathway by monaurally reducing sensory input. The aim of this study was to characterise the changes in electrophysiological and vascular function associated with this asymmetric lesioning. Depth electrodes located in the inferior colliculi were used to measure wave II and IV of the auditory evoked response (AER) and collicular blood flow. These were measured up to eight days after DNB exposure in rats, in which preexisting reduction in sensory input in one ear was achieved by tympanic membrane rupture. Significant increases of between 14-27 dB were seen in the mean stimulus level required to generate a 50% isoamplitude response for wave IV in the intact (ie vulnerable) pathway over days 1-8 post DNB. No significant changes in this response for the other AER waves were seen over the same recording period. Significant increases in blood flow were seen in the inferior colliculi up to 24 hours after the final dose of DNB. Differences in increased flow between the colliculi were also highly significant, with peak increases of 200% and 80% seen in the intact and protected sides respectively. This difference shows that DNB enhanced blood flow appears to reflect the severity of the DNB induced functional deficit. In both cases, disturbance to normal glial function in maintaining K+ homeostasis, may underlie the neurophysiological deficit and the increase in blood flow seen at the level of the inferior colliculi. These asymmetric functional changes were also parallelled by the differential lesion severity between the protected and unprotected pathways. Hence, protection against DNB glial lesion severity by reduction in sensory input, and consequently metabolic demand, is paralleled by the early vascular response and functional neuronal deficit seen over the eight day post DNB recording period.

Acoustic Stimulation↗
PubMed1988

Glycine-like immunoreactivity in the rat auditory pathway.

From neurophysiological and biochemical studies it has been suggested that glycine can function as a major inhibitory neurotransmitter in the central nervous system of mammals. In the present study, anti-glycine antiserum was obtained from rabbits immunized with glycine conjugated to rabbit serum albumin via glutaraldehyde and purified by affinity chromatography. The antibody thus obtained was found specific for glycine as determined by an enzyme immunoassay system. The immunocytochemical distribution of glycine in the auditory tract and internal ear was investigated with the antibody. In the central auditory pathway, glycine-like immunoreactivity was mainly located in the ventral and dorsal cochlear nuclei, trapezoid body, lateral lemniscus and inferior colliculus. In the labyrinth, immunoreactivity was detected in the vestibular ganglion and the supporting cells of the crista ampullaris and the organ of Corti, but not in the spiral ganglion. These findings suggest an important role of glycine in the auditory and vestibular pathways.

Animals↗
PubMed2000

KCNQ4, a K+ channel mutated in a form of dominant deafness, is expressed in the inner ear and the central auditory pathway.

Mutations in the potassium channel gene KCNQ4 underlie DFNA2, an autosomal dominant form of progressive hearing loss in humans. In the mouse cochlea, the transcript has been found exclusively in the outer hair cells. By using specific antibodies, we now show that KCNQ4 is situated at the basal membrane of these sensory cells. In the vestibular organs, KCNQ4 is restricted to the type I hair cells and the afferent calyx-like nerve endings ensheathing these sensory cells. Several lines of evidence suggest that KCNQ4 underlies the I(K,n) and g(K,L) currents that have been described in the outer and type I hair cells, respectively, and that are already open at resting potentials. KCNQ4 is also expressed in neurons of many, but not all, nuclei of the central auditory pathway, and is absent from most other brain regions. It is present, e.g., in the cochlear nuclei, the nuclei of the lateral lemniscus, and the inferior colliculus. This is the first ion channel shown to be specifically expressed in a sensory pathway. Moreover, the expression pattern of KCNQ4 in the mouse auditory system raises the possibility of a central component in the DFNA2 hearing loss.

Amino Acid Sequence↗
PubMed1993

The binaural auditory pathway: membrane currents limiting multiple action potential generation in the rat medial nucleus of the trapezoid body.

In this paper we describe the membrane currents of neurons in the medial nucleus of the trapezoid body (MNTB), which serves as an inverting relay in the binaural auditory pathway. In the following paper (Forsythe & Barnes-Davies (Proc. R. Soc. Lond. B 251, 151 (1993))) we describe the synaptic inputs to the MNTB and discuss the significance of these results for transmission through this nucleus, where the fidelity of information transfer will depend on the integration of synaptic responses with the intrinsic postsynaptic membrane properties. Whole-cell patch clamp recordings were made from MNTB neurons using a thin-slice preparation of the rat brain stem. Resting potentials were -70 mV with a neuronal input resistance of 250 M omega and a membrane time constant of 14 ms. Voltage-clamp studies showed that MNTB neurons possess an inward sodium current, an outward current similar to a delayed rectifier and an inward rectifier. In addition, a novel transient outward current exhibiting rapid kinetics and a sustained current are present, which are both blocked by micromolar concentrations of 4-aminopyridine (4AP). Current-clamp recording showed that MNTB neurons respond to depolarization with a single overshooting action potential (AP); 4AP blocked a fast after-hyperpolarization, increased AP duration, and converted the single AP response on depolarization to a train of action potentials.

4-Aminopyridine↗