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Functioning of the brain-stem auditory pathway in non-retarded autistic individuals.

Functioning of auditory brain-stem pathways was examined in non-retarded autistic individuals (14-28 years of age). Functioning was assessed by recording ERPs (event-related brain potentials) generated by these auditory pathways. These ERPs were evoked by click stimuli and occurred within the first 8 msec following the onset of the click. To assess the ability of these early auditory pathways to process sensory stimuli of varying characteristics, we systematically varied click intensity, rate of stimulation, ear of stimulation, and polarity of clicks. The results show that non-retarded autistic individuals have normal functioning of the brain-stem auditory pathways which generate these ERPs: every autistic subject had normal ERPs. So, disorder in auditory brain-stem pathways which generate these ERPs is not necessary for autism to occur. The dysfunctioning neural systems directly responsible for autism in non-retarded individuals must be sought elsewhere. Ten of the autistic subjects in this study, whom we found to have normal auditory brain-stem ERPs, had previously been found to have abnormalities in longer latency cognitive ERP components (Courchesne et al. 1984, 1985). We conclude, therefore, that those abnormalities in longer latency components are not the downstream consequences of abnormalities in the structures generating the auditory brain-stem ERPs recorded in the present study.

Adolescent

Localization of callosal auditory pathways: a CT case study.

The position of the auditory pathways in the human corpus callosum has not been defined by modern imaging techniques. We report a case with a discrete hemorrhagic lesion in the posterior body of the corpus callosum. The only signs of disturbed callosal function were limited to the auditory system--suppression of left ear stimuli with dichotic listening and neglect of left-sided auditory simultaneous stimuli.

Adult

Organization of the auditory pathway in the thoracic ganglia of noctuid moths.

We describe the neuroarchitecture of the noctuid thoracic nerve cord and use this framework to interpret the organization of the auditory pathway responsible for escape behaviour in noctuid moths. Noctuid moths possess only two auditory receptors (A1, A2), in each ear. The axon of the A1 cell projects initially to a glomerulus located ventrally and medially in the metathoracic ganglion, where it bifurcates. One branch ascends in the ventral intermediate tract to the brain, the other descends in the ventral intermediate tract into abdominal neuromeres of the metathoracic ganglion. Both axons arborize in the median ventral and ring tracts in each neuromere. The central projections of the A2 cell remain largely within the metathoracic ganglion. The axon bifurcates at the midline and directs arborizations dorsally to the dorsal intermediate and median dorsal tracts, and ventrally into the ring tract where the arborizations overlap those of the A1 afferent. The afferent projections remain ipsilateral to the ear of origin. We describe a posterior auditory association area in the metathoracic ganglion in which the major arborizations of several identified interneurones overlap those of the A1 afferent and make monosynaptic connections with it. These interneurones all respond tonically to sound stimuli. We have also identified the projections of the A1 afferent, interneurones, and motor neurones in the segmentally equivalent anterior auditory association area of the mesothoracic ganglion. An interneurone with major arborizations in the same tracts as the A1 afferent, and receiving monosynaptic input from it, is described. The arborizations of higher order interneurones lie mainly in dorsal tracts along with those of flight motor neurones. All the interneurones in this anterior centre respond phasically or phasic/tonically to sound stimuli. The relevance of this anatomical organization for predator avoidance behaviour is considered and the organization of auditory pathways in tympanate insects compared.

Animals

Distribution of Fos-like immunoreactivity in the auditory pathway of the Sprague-Dawley rat elicited by cochlear electrical stimulation.

Fos-like immunoreactivity (FLI) was mapped in the auditory pathway of Sprague-Dawley rats in response to unilateral electrical stimulation of the cochlea implanted with two stimulating electrodes. Densely packed FLI neurons were widely distributed in the dorsal cochlear nucleus (more ipsilaterally than contralaterally), while FLI neurons were rare in the posteroventral cochlear nucleus and virtually absent in the anteroventral cochlear nucleus. Sparse FLI was detected in the superior olivary complex, the pontine nuclei and the ipsilateral dorsal nucleus of the lateral lemniscus, whereas the contralateral dorsal nucleus of the lateral lemniscus was moderately labeled. In the inferior colliculus, the pattern of FLI was similar on both sides, restricted mainly to its dorsal and external cortices. At the thalamic level, FLI neurons were seen in the dorsal and medial divisions of the medial geniculate body as well as in the peripeduncular nucleus. A significant increase of FLI was observed in the temporal cortex. This study demonstrates the presence of selective functional changes along the auditory pathway elicited by electrical stimulation of the cochlea, as revealed by FLI.

Acoustic Stimulation

Activity elicited in the auditory pathway of the rat by electrical stimulation of the cochlea.

The activity elicited by electrical stimulation of the cochlea in the auditory pathway was assessed in an animal model of cochlear implants on the basis of the induction of the immediate early gene c-fos and single neuron recordings. Electrical stimulation of the cochlea induced Fos-like immunoreactivity in the cochlear nucleus, mainly in its dorsal nucleus, in the superior olivary complex, in the lateral lemniscus, but not in the central nucleus of the inferior colliculus, the main relay nucleus in the auditory midbrain. However, single unit recordings from the inferior colliculus, ipsilateral and contralateral to the electrically stimulated cochlea, showed clear responses of single neurons, reminiscent of those elicited by acoustic stimulation. These findings provide immunocytochemical and electrophysiological evidence that the various nuclei of the auditory pathway are activated by electrical stimulation of the cochlea.

Animals

Organization of ascending auditory pathways in the pigeon (Columba livia) as determined by autoradiographic methods.

A mixture of tritiated proline and fucose was injected into the labyrinthine endolymphatic space of 5 white king pigeons (Columba livia). Using standard autoradiographic techniques, we observed transsynaptic labeling in ascending auditory pathways to the level of the mesencephalon. Auditory system structures, ipsilateral to the injection site, which labeled heavily were the cochlear nerve, the magnocellular and angular nuclei, and the superior olive. Those ipsilateral structures which were slightly labeled were the lateral lemniscus and the dorsal part of the lateral mesencephalic nucleus. Contralateral structures which labeled were the superior olive, lateral lemniscus, and dorsal part of the lateral mesencephalic nucleus. The results of this study suggest that ascending auditory pathways (to the level of the mesencephalon) in the pigeon are more similar to those described for mammals in general than previously thought.

Abducens Nerve

Hereditary dysfunction of the brain stem auditory pathways as the major cause of speech retardation.

Grossly abnormal auditory brain stem responses (ABR) and abnormally high stapedius reflex thresholds were found in 2 pairs of siblings, not akin. Pure tone audiometry showed moderate to moderately severe hearing impairment in all 4 subjects, but neither the ABR findings nor the stapedius reflex thresholds were compatible with pure cochlear lesions. In all the cases the benefit from using hearing aids was conspicuously poor, and the development of oral language markedly retarded, one pair of siblings being essentially incapable of oral--aural communication. A cousin to one of the pairs of siblings showed similar but less pronounced symptoms and signs. Intelligence was judged to be normal in all 5 individuals and neurologic examination did not reveal CNS abnormalities besides the hearing impairment. We assume dysfunction of the brain stem auditory pathways to be the main cause of the speech retardation in the 2 pairs of siblings and the abnormality to be hereditary in nature.

Adolescent

[Characteristics of the reactions of neurons of successive links in the auditory pathway to changes in the timing of acoustic signals].

Afferent impulsation was compared for different levels of the auditory system: the cochlear nuclei, posterior colliculi, and the auditory cortex. While moving from the cochlear nuclei over to the posterior colliculi and the auditory cortex, the number of neurons describing the temporal structure of the amplitude-modulated signal's envelope in the impulse activity pattern, becomes sharply reduced; the number of neurons selectively responding to certain phases of the envelope increases; the firing rate of neurons of the auditory pathway's higher levels decreases; the repetition rates becomes narrow due to limitation from both the high- and the low-frequency sides. Selectivity of responses to combination of such signal parameters as the frequency of the carrier and the rhythm of the amplitude modulation, increases. Specificity of the neuronal responses increases on certain combinations of such parameters of the frequency-modulated sounds as the frequency range in the signal, the direction and speed of the frequency modulation. The data obtained revealed some general tendencies of the impulsation transformation in successive levels of the auditory pathway.

Animals

Network analysis of functional auditory pathways mapped with fluorodeoxyglucose: associative effects of a tone conditioned as a Pavlovian excitor or inhibitor.

The purpose of this study was to examine how opposite learned associative properties of the same auditory stimulus are represented by the pattern of network interactions between auditory system structures. [14C(U)]2-fluoro-2-deoxyglucose (FDG) autoradiography was used to compare mean auditory system activity and interregional correlations resulting from the presentation of a tone trained as either a Pavlovian conditioned excitor or inhibitor. Rats were trained with reinforced trials of the conditioned excitor (A+) intermixed with non-reinforced trials of a tone-light compound (AX-). For the Conditioned Excitor group, the tone was the excitor (A+), while for the Conditioned Inhibitor group the tone was the inhibitor (X-). After conditioning, both groups were injected with FDG and presented with the same tone. Structural equation models, constructed from the anatomical connections between auditory regions and their interregional correlations in FDG uptake, were used to calculate path coefficients representing the network interactions. The opposite associative significance of the tone was reflected as functional changes in the interactions between parallel auditory pathways. Direct covariance effects through lemniscal pathways from the ventral cochlear nucleus were similar in absolute magnitude but differed in sign between the Excitor and Inhibitor network models. Extra-auditory influences on the dorsal cochlear nucleus were greater for the tone-inhibitor, reflecting possible interactions of this nucleus with extra-auditory regions. The different associative effects of the tone suggest that central auditory pathways can code not only the physical qualities, but also the associative significance of auditory stimuli. These findings demonstrate that neural network interactions differentiate the associative effects of tones in the brain. It is proposed that associative learning is a distributed property of neural networks and that such a property can be understood by considering the interactions between component parts of the network.

Acoustic Stimulation

GAD- and GABA-immunoreactivity in the ascending auditory pathway of horseshoe and mustached bats.

A comparative study of the immunostain to antibodies directed against glutamic acid decarboxylase (GAD) and gamma-aminobutyric acid (GABA) in the ascending auditory pathway was carried out in horseshoe bats (Rhinolophus rouxi) and mustached bats (Pteronotus parnellii). In both species GAD/GABA-positive puncta (presumed axonal boutons) and GAD/GABA-positive cells were found in the cochlear nucleus, the superior olivary complex, the nuclei of the lateral lemniscus the inferior colliculus, and the medial geniculate body. General features of the immunostaining pattern in the auditory pathway agree with observations in other mammals. Quantitative analysis of puncta distribution shows that many auditory centers are characterized by subregional differences in puncta density and distribution. This indicates local differences in putatively inhibitory input related to connectivity and tonotopic organization. The following species characteristic features were found: 1) The dorsal non-laminated portion of the dorsal cochlear nucleus in horseshoe bats lacks the GAD/GABA-immunoreactive cells typical for the ventral laminated portion and the dorsal cochlear nucleus of other species. Clearly, a cytoarchitectonic specialization is accompanied by a loss of putatively GABAergic local inhibitory circuits. 2) The ventral division of the medial geniculate body of the mustached bat lacks GAD/GABA-immunopositive cells. Such cells are present in the horseshoe bat and other mammals. This finding implies functional differences in the organization of the medial geniculate body within the same mammalian order.

Animals

Avian auditory pathways show met-enkephalin-like immunoreactivity.

Pathways associated with a recently defined region of the avian auditory thalamus, the shell of the nucleus ovoidalis (Ov), were examined for met-enkephalin immunoreactivity. The presence of enkephalin-like immunoreactive (ELI) perikarya within the medial margin of the inferior colliculus (ICM), afferent to the Ov shell, implicated ICM as a source of ELI fibers within the Ov shell and tract. The shell also contained ELI perikarya and its targets, including the ventromedial hypothalamus and caudoventral paleostriatal complex, were characterized by ELI fields. These data suggest that enkephalinergic auditory pathways, in parallel with traditionally recognized auditory projections, target regions of the avian basal forebrain.

Animals

Electrically induced fos-like immunoreactivity in the auditory pathway of the rat: effects of survival time, duration, and intensity of stimulation.

The goal of the present study was to establish how Fos-like immunoreactivity (FLI) elicited in the rat auditory pathway by unilateral electric stimulation of the cochlea is affected by the following experimental parameters: duration and intensity of stimulation, duration of survival time after offset of stimulation. The dense FLI found in the ipsilateral dorsal cochlear nucleus, as well as the moderate FLI found in the contralateral dorsal cochlear nucleus and in the posteroventral cochlear nucleus on both sides, were consistent after survival times ranging from 0 to 2-3 h, but they significantly decreased after longer survival times (5 and 6 h). In the same nuclei, FLI was increased even by short durations of stimulation (5 and 10 min) as compared to control rats, although FLI progressively increased for longer stimulation (20 and 45 min). In the auditory thalamus, FLI was found mainly in the peripeduncular nucleus, the dorsal and medial divisions of the medial geniculate body, whereas its ventral division was virtually devoid of immunoreactive neurons. This pattern of FLI distribution in the auditory thalamus persisted even after relatively long survival times (5 and 6 h). In both the cochlear nucleus and auditory thalamus, the density of FLI slightly increased in parallel with the intensity of stimulation. In other auditory nuclei, such as the inferior colliculus and the nucleus of the lateral lemniscus, there was no simple relation between the density of FLI and the three tested experimental parameters. Thus, the distribution and density of FLI did not vary in parallel in the various nuclei of the auditory pathway as a function of the tested experimental parameters; different patterns of FLI changes were instead observed in different auditory nuclei.

Action Potentials

Visual projections induced into the auditory pathway of ferrets: II. Corticocortical connections of primary auditory cortex.

Although the development of corticocortical projections has been well studied, less is known about the role of sensory inputs in the specification of these connections. As part of an ongoing series of studies in our laboratory, we have examined the role of thalamic input modality in the development of corticocortical connections. These studies involve making unilateral lesions and inducing retinal inputs into the auditory thalamus (MGN) during early development in ferrets, thereby conferring visual responsiveness on primary auditory cortex (AI). In this way we can examine the role of input identity in cortical specification in general, and connectivity patterns specifically. A previous paper (Pallas et al. [1990] J. Comp. Neurol. 298:50-68) described the pattern of thalamocortical and corticothalamic connections of auditory cortex in normal and lesioned animals. This study compares the pattern of auditory corticocortical connections in normal and lesioned animals. We injected neuroanatomical tracers into AI and mapped out the distribution of retrogradely labelled cells in the cortex. We report that the cortical inputs to ferret AI resembled those in cats, and that the pattern of ipsi- and contralateral corticocortical connections of ferret AI with visual input was similar to the normal pattern. Auditory cortex with visual input did not make ectopic connections with visual cortex, but maintained its connections with other auditory cortical areas. These results suggest that the overall corticocortical connections of an area are not influenced by the modality or activity pattern of its inputs. In particular, altering the input activity to a cortical area does not seem to promote the formation of entirely new connections, although small changes in the strength of existing connections are possible (Sur et al. [1990] Trends Neurosci. 13:227-233).

Animals

The effects of long-term cochlear hearing loss on the functional organization of central auditory pathways.

We have developed an animal model of neonatal high-frequency cochlear hearing loss to investigate the long-term effects on the central auditory pathways. Specifically, we have induced basal cochlear lesions in newborn kittens using the ototoxic aminoglycoside, amikacin. We have monitored the consequent auditory threshold elevations using auditory brainstem evoked responses (ABR) to tone pip stimuli. In the mature animal we have mapped tonotopic (cochleotopic) representation in primary auditory cortex (AI) using standard micro-electrode recording techniques, and we show that this map becomes massively re-organized. In particular, one frequency area that corresponds to the high frequency cut-off slope of the subject's audiogram appears to become greatly expanded, in some cases to take up 75% of AI surface. In general, the development of normal cochleotopic or tonotopic representation in cortex appears to depend upon the integrity of ascending sensory input from the cochlea particularly during early stages of development. With the clinician in mind, we discuss our findings in relation to practical issues.

Acoustic Stimulation

Effects of aircraft noise on hearing and auditory pathway function of school-age children.

This study was conducted to investigate the influence of high-frequency aircraft noise on the function of the auditory system of school-age children. A total of 228 students attending a school near an airport (school A) and 151 students attending a school far from an airport (school B) were analyzed. Audiometry and brainstem auditory evoked potential (BAEP) detection were performed in all subjects to evaluate cochlear and retrocochlear function. The results of audiometry indicated that hearing ability was significantly worse in the children of school A, which was located under the flight paths. The values of pure tone average, high pure tone average, and threshold at 4 kHz were all higher in children who were frequently exposed to aircraft noise. There was no consistent difference in BAEP latencies between the two schools. These results indicate that central transmission is not affected in children who have been exposed to aircraft noise for several years. The results of the present study showed a significant association between aircraft noise exposure and prevalence of noise-induced hearing loss. Although damage to peripheral cochlear organs was confirmed in school-age children, involvement of the central auditory pathway could not be verified.

Aircraft

Functional network interactions between parallel auditory pathways during Pavlovian conditioned inhibition.

Using covariance structural equation modeling and fluorodeoxyglucose (FDG) autoradiography this study examined auditory system interactions when the learned associative effects of a tone were inhibited by a light. Two groups of rats received pairings of a tone (conditioned excitor: T+) with a mild footshock. Group TL- was trained in a Pavlovian conditioned inhibition paradigm (T+/TL-) where the tone-light compound signaled the absence of footshock, making the light the inhibitor (L-). Group TL degree was trained with the tone as the excitor and the light as a 'neutral' stimulus. After FDG injection, all rats were presented with the tone-light compound. Group differences in auditory system FDG uptake were observed only in the ventral division medial geniculate nucleus (MGV), where group TL- had relatively lower incorporation. Structural equation modeling was used with the covariances of FDG activity to determine the functional influences through the auditory system anatomic connections. Differences were noted mainly at the level of the inferior colliculus (IC) and medial geniculate, possibly reflecting the unique anatomic relation of these regions with extraauditory areas. Ascending and descending influences from the IC differed with stronger influences for group TL-. Intracollicular and the ascending influence influences of MGV and medial division of the medial geniculate nucleus (MGM) on the auditory cortex also differed mainly in the sign of the functional interaction. These results demonstrate how interactions among parallel auditory pathways can code the behavioral significance of auditory stimuli and emphasize that a full appreciation of neural operations underlying learning can only be gained through examination of both regional activity and interregional interactions.

Animals

[The auditory pathway in guinea pigs. A [14C]2-deoxyglucose study (author's transl)].

The auditory pathway of guinea pigs was labeled with [14C]-deoxyglucose after mon- or binaural stimulation with farfield white noise in a sound-proof chamber. In the autoradiographs, all auditory nuclei were labeled. The highest metabolic effects were seen in the dorsal cochlear nucleus, the lateral superior olivary nucleus, and in the inferior colliculus. No selective labeling was observed in the auditory cortex. Monaural stimulation depressed the metabolic activity contralaterally in the ventral cochlear nucleus and ipsilaterally in the medial nucleus of the trapezoid body, the dorsomedial periolivary nucleus, and in the inferior colliculus.

Acoustic Stimulation

Assessment of functional integrity of brain stem auditory pathways by stimulus stress.

The effect of increasing the repetition rate of click stimuli on auditory brain stem responses has been studied in young subjects with normal hearing, in old people and in patients with multiple sclerosis. The most conspicuous effects have been observed in the amplitude of the responses, especially waves II and V, and in the value of the brain stem conduction time. Increased stimulation rates may serve as a method for the assessment of the functional status of the lower auditory pathways in diverse pathological conditions.

Acoustic Stimulation