Noninvasive fMRI Investigation of Interaural Level Difference Processing in the Rat Auditory Subcortex

Binaural hearing improves performance in most auditory tasks and is essential for some. This paper introduces the brain stem pathways and nuclei involved in binaural interaction and outlines some recent approaches to understanding binaural mechanisms. It also provides examples of basic science approaches to the effects of infant hearing loss on those pathways and mechanisms. Binaural interaction occurs primarily and almost simultaneously at three levels of the brain: the superior olivary complex (SOC), the nuclei of the lateral lemniscus (NLL) and the inferior colliculus (IC). The SOC derives its input from the anterior ventral cochlear nucleus (CN) through branching axons that innervate several SOC subdivisions on both sides of the brain. At least some of these anteroventral CN axons project on up to the contralateral NLL and IC. The IC and NLL also receive direct, major projections from the contralateral CN, via the dorsal and intermediate acoustic striae, and from the SOC bilaterally. The IC receives additional input from the NLL bilaterally, and is thus innervated by every nuclear group within the auditory brain stem. There is little evidence for strict, functional segregation in these binaural pathways, although subdivisions of the SOC appear to be predominantly involved in analysing either interaural time or level differences (ITD, ILD). ITD- and ILD-sensitive neurones are also found in abundance in the central IC. There is emerging evidence that binaural information is coupled with spectral cues derived from the outer ear in several auditory mid-brain regions [the NLL, the external IC and the superior colliculus (SC)] to produce topographic representations of auditory space. Throughout the higher auditory system the response of neurones to stimulation of each ear is either excitatory or inhibitory, and there is a spatial segregation of neurones receiving predominantly excitatory or inhibitory input from the ipsilateral ear in both the medial geniculate body of the thalamus and the auditory cortex. Neonatal, unilateral hearing loss leads to a rearrangement of binaural connections in the auditory brain stem, to changes in the physiology of IC neurones in response to stimulation of the normal ear and to compensatory alterations in the auditory space map in the SC. The same hearing losses in adulthood do not produce these changes. The evidence from this and other work suggests that binaural mechanisms are more sensitive to hearing loss, over a longer developmental period, than mechanisms subserving monaural processing.

With the exception of low‐frequency characteristic frequency (CF) units, the ipsilaterally evoked discharge of the majority of S‐segment cells can be inhibited with simultaneous stimulation of the contralateral ear. The contralateral inhibitory CF is usually identical to the ipsilateral excitatory CF. The width of the contralateral inhibitory tuning curve is similar to the width of the ipsilateral excitatory tuning curve. Partial inhibition of the ipsilaterally evoked discharge increases the interspike intervals and increases the variability of the discharge. Inhibition, like excitation, is tonically acting. The contralateral inhibitory input with equally intense tones (measured in terms of decibels above threshold) is either about as effective as the excitatory input or less effective, rarely more effective. The primary factor determining the spike output from S‐segment cells is not the absolute intensity level of the stimulus but rather the relative intensity difference of the stimulus at the two ears. [Work supported in part by National Institutes of Health, U. S. Department of Health, Education, and Welfare.]

Single-sided deafness (SSD) induces cortical neural plastic changes according to duration of deafness. However, it is still unclear how the auditory cortical changes accompany the subcortical neural changes. The present study aimed to find the neural plastic changes in the cortical and subcortical auditory system following adult-onset single-sided deafness (SSD) using Mn-enhanced magnetic resonance imaging (MEMRI). B57BL/6 mice (postnatal 8-week-old) were divided into three groups: the SSD-4-week group (postnatal 12-week-old, n = 11), the SSD-8-week group (postnatal 16-week-old, n = 11), and a normal-hearing control group (postnatal 8-week-old, n = 9). The left cochlea was ablated in the SSD groups. White Gaussian noise was delivered for 24 h before MEMRI acquisition. T1-weighted MRI data were analyzed from the cochlear nucleus (CN), superior olivary complex (SOC), lateral lemniscus (LL), inferior colliculus (IC), medial geniculate body (MG), and auditory cortex (AC). The differences in relative Mn2+-enhanced signal intensities (Mn2+SI) and laterality were analyzed between the groups. Four weeks after the SSD procedure, the ipsilateral side of the SSD showed significantly lower Mn2+SI in the CN than the control group. On the other hand, the contralateral side of the SSD demonstrated significantly lower Mn2+SI in the SOC, LL, and IC. These decreased Mn2+SI values were partially recovered at 8 weeks after the SSD procedure. The interaural Mn2+SI differences representing the interaural dominance were highest in CN and then became less prominently higher in the auditory neural system. The SSD-8-week group still showed interaural differences in the CN, LL, and IC. In contrast, the MG and AC did not show any significant intergroup or interaural differences in Mn2+SI. In conclusion, subcortical auditory neural activities were decreased after SSD, and the interaural differences were diluted in the higher auditory nervous system. These findings were attenuated with time. Subcortical auditory neural changes after SSD may contribute to the change in tinnitus severity and the outcomes of cochlear implantation in SSD patients.

The auditory system uses three cues to decode sound location: interaural time differences (ITDs), interaural level differences (ILDs), and spectral notches (SNs). Initial processing of these cues is done in separate brainstem nuclei, with ITDs in the medial superior olive, ILDs in the lateral superior olive, and SNs in the dorsal cochlear nucleus. This work addresses the nature of the convergence of localization information in the central nucleus of the inferior colliculus (ICC). Ramachandran et al. (1999) argued that ICC neurons of types V, I, and O, respectively, receive their predominant inputs from ITD-, ILD-, and SN-sensitive brainstem nuclei, suggesting that these ICC response types should be differentially sensitive to localization cues. Here, single-unit responses to simultaneous manipulation of pairs of localization cues were recorded, and the mutual information between discharge rate and individual cues was quantified. Although rate responses to cue variation were generally consistent with those expected from the hypothesized anatomical connections, the differences in information were not as large as expected. Type I units provide the most information, especially about SNs in the physiologically useful range. Type I and O units provide information about ILDs, even at low frequencies at which actual ILDs are very small. ITD information is provided by a subset of all low-frequency neurons. Type V neurons provide information mainly about ITDs and the average binaural intensity. These results are the first to quantify the relative representation of cues in terms of information and suggest a variety of degrees of cue integration in the ICC.

Neurotransmitter and neuromodulator systems of the rat inferior colliculus and auditory brainstem studied by in situ hybridization

How does the brain accomplish sound localization with invariance to total sound level? Sensitivity to interaural level differences (ILDs) is first computed at the lateral superior olive (LSO) and is observed at multiple levels of the auditory pathway, including the central nucleus of inferior colliculus (ICC) and auditory cortex. In LSO, this ILD sensitivity is level-dependent, such that ILD response functions shift toward the ipsilateral (excitatory) ear with increasing sound level. Thus early in the processing pathway changes in firing rate could indicate changes in sound location, sound level, or both. In ICC, while ILD responses can shift toward either ear in individual neurons, there is no net ILD response shift at the population level. In behavioral studies of human sound localization acuity, ILD sensitivity is invariant to increasing sound levels. Level-invariant sound localization would suggest transformation in level sensitivity between LSO and perception of sound sources. Whether this transformation is completed at the level of the ICC or continued at higher levels remains unclear. It also remains unknown whether perceptual sound localization is level-invariant in rats, as it is in humans. We asked whether ILD sensitivity is level-invariant in rat auditory cortex. We performed single-unit and whole cell recordings in rat auditory cortex under ketamine anesthesia and measured responses to white noise bursts presented through sealed earphones at a range of ILDs. Surprisingly, we found that with increasing sound levels ILD responses shifted toward the ipsilateral ear (which is typically inhibitory), regardless of whether cells preferred ipsilateral, contralateral, or binaural stimuli. Voltage-clamp recordings suggest that synaptic inhibition does not contribute substantially to this transformation in level sensitivity. We conclude that the level invariance of ILD sensitivity seen in behavioral studies is not present in rat auditory cortex.

The organization of the auditory brainstem in adult, darkly pigmented ferrets was studied by using the retrograde transport of the lectin wheat germ agglutinin-horseradish peroxidase injected into one inferior colliculus. Retrogradely labelled neurons were found bilaterally in every nucleus of the auditory brainstem. The greatest number of labelled neurons was found in the cochlear nuclei contralateral to the injection site, the ipsilateral medial superior olivary nucleus, both lateral superior olivary nuclei, the ipsilateral ventral nucleus of the lateral lemniscus, both dorsal nuclei of the lateral lemniscus, and the contralateral inferior colliculus. Quantitative assessment of the projections from the cochlear nuclei showed that the number of contralaterally projecting neurons exceeded the number of ipsilaterally projecting neurons by about 50 to one. This ratio remained relatively stable over a wide range of volumes of injected lectin, whereas the absolute number of labelled neurons on each side varied by at least twofold for a constant volume of lectin. These results provide basic data on the ferret auditory system and demonstrate quantitatively some properties of the projections between the cochlear nucleus and the inferior colliculus.

Sound localisation is defined as the ability to identify the position of a sound source. The brain employs two cues to achieve this functionality for the horizontal plane, interaural time difference (ITD) by means of neurons in the medial superior olive (MSO) and interaural intensity difference (IID) by neurons of the lateral superior olive (LSO), both located in the superior olivary complex of the auditory pathway. This paper presents spiking neuron architectures of the MSO and LSO. An implementation of the Jeffress model using spiking neurons is presented as a representation of the MSO, while a spiking neuron architecture showing how neurons of the medial nucleus of the trapezoid body interact with LSO neurons to determine the azimuthal angle is discussed. Experimental results to support this work are presented.

Antisera to GAD (glutamic acid decarboxylase) and GABA were used to determine the distribution of GABAergic cells and terminals in the brainstem and midbrain auditory nuclei of the barn owl. The owl processes time and intensity components of the auditory signal in separate pathways, and each pathway has a distinctive pattern of GAD- and GABA-like immunoreactivity. In the time pathway, all the cells of the cochlear nucleus magnocellularis and nucleus laminaris receive perisomatic GABAergic terminals, and small numbers of GABAergic neurons surround both nuclei. The ventral nucleus of the lateral lemniscus (anterior division) contains both immunoreactive terminals and some GABAergic neurons. In the intensity pathway, dense immunoreactive terminals are distributed throughout the cochlear nucleus angularis, which also contains a small number of GABAergic neurons. The superior olive contains two GABAergic cell types and immunoreactive terminals distributed throughout the neuropil. All the neurons of the nucleus of the lateral lemniscus (ventral part) appear to be GABAergic, and this nucleus also contains a moderate number of immunoreactive terminals. Immunoreactive terminals are distributed throughout the neuropil of the ventral nucleus of the lateral lemniscus (posterior division), whereas multipolar and small fusiform GABAergic neurons predominate in the dorsal regions of the nucleus. The time and intensity pathways combine in the inferior colliculus. The central nucleus of the inferior colliculus contains a larger number of fusiform and stellate GABAergic neurons and a dense plexus of immunoreactive terminals, whereas the external nucleus contains slightly fewer immunoreactive cells and terminals. The superficial nucleus contains dense, fine immunoreactive terminals and a small number of GABAergic neurons.

Distribution of glutamatergic, GABAergic, and glycinergic neurons in the auditory pathways of macaque monkeys

Two sources of inhibition affecting binaural evoked responses in the rat's inferior colliculus : the dorsal nucleus of the lateral lemniscus and the superior olivary complex

Plastic Changes in Glycine and GABA Release and Uptake in Adult Brain Stem Auditory Nuclei after Unilateral Middle Ear Ossicle Removal and Cochlear Ablation

Interaural level differences (ILDs) provide salient cues for localizing high-frequency sounds in space, and populations of neurons that are sensitive to ILDs are found at almost every synaptic level from brain stem to cortex. These cells are predominantly excited by stimulation of one ear and predominantly inhibited by stimulation of the other ear, such that the magnitude of their response is determined in large part by the intensities at the 2 ears. However, in many cases ILD sensitivity is also influenced by overall intensity, which challenges the idea of unambiguous ILD coding. We investigated whether ambiguity is reduced from one synaptic level to another for 2 centers in the so-called ILD processing pathway. We recorded from single cells in the free-tailed bat lateral superior olive (LSO), the first station where ILDs are coded, and the central nucleus of the inferior colliculus (ICC), which receives a strong projection from the LSO, as well as convergent projections from many other auditory centers. We assessed effects of overall intensity by comparing ILD functions generated with different fixed intensities to the excitatory ear. LSO cells were characterized by functions that shifted in a systematic manner with increasing intensity to the excitatory ear. In contrast, significantly more ICC cells had functions that were stable across overall sound intensity, indicating that hierarchical transformations increase stability. Furthermore, a population analysis based on proportion of active cells indicated that stability in the ICC was greatly enhanced when overall population activity was considered.

Sound localization is an important aspect of auditory scene analysis, allowing listeners to group acoustic components from the same location into a single stream (Bregman 1990). Binaural pitch fusion, the fusion of different frequency tones across ears, can be thought of as one type of auditory streaming. Little is known about how sound localization cues affect binaural fusion. The goal of this study was to investigate the effects of interaural level differences (ILDs), one cue for sound localization, on binaural fusion of dichotic tones. Binaural pitch fusion was measured in adult normal-hearing (NH) listeners, using five ILD conditions: ILD = 0, 1.25, 2.5, 5, and 10 dB. Fusion ranges were measured by simultaneous presentation of reference and comparison stimuli in opposite ears, and varying the comparison stimulus to find the frequency range that fused with the reference stimulus. Preliminary results (5 NH; data collection is ongoing) show that small ILDs increase fusion ranges, while larger ILDs decrease fusion ranges. These findings suggest that ILDs can affect fusion range in NH listeners, and imply that simulated sound source location may provide a top-down grouping cue for binaural fusion. [This research was funded by a NIH-NIDCD grant R01 DC013307.]Sound localization is an important aspect of auditory scene analysis, allowing listeners to group acoustic components from the same location into a single stream (Bregman 1990). Binaural pitch fusion, the fusion of different frequency tones across ears, can be thought of as one type of auditory streaming. Little is known about how sound localization cues affect binaural fusion. The goal of this study was to investigate the effects of interaural level differences (ILDs), one cue for sound localization, on binaural fusion of dichotic tones. Binaural pitch fusion was measured in adult normal-hearing (NH) listeners, using five ILD conditions: ILD = 0, 1.25, 2.5, 5, and 10 dB. Fusion ranges were measured by simultaneous presentation of reference and comparison stimuli in opposite ears, and varying the comparison stimulus to find the frequency range that fused with the reference stimulus. Preliminary results (5 NH; data collection is ongoing) show that small ILDs increase fusion ranges, while larger ILDs decrea...

Ascending projections of the cochlear nuclei in the mustache bat were analyzed by anterograde transport of [3H]-leucine and by retrograde transport of HRP. We were particularly interested in pathways to two parts of the system: (1) to the medial superior olive, because this nucleus is missing in most echolocating bats, but appears to be present in the mustache bat, and (2) to the intermediate and ventral nuclei of the lateral lemniscus, because these nuclei are hypertrophied and highly differentiated in all echolocating bats that we have examined. The results show a highly systematic projection from the anteroventral cochlear nucleus to all of the auditory nuclei in the brain stem. After an injection of [3H]-leucine in the anterior and dorsal part of the anteroventral cochlear nucleus, presumably in a region sensitive to low frequencies, label is seen in the following locations: ipsilateral to the injection in the lateral part of the lateral superior olive; bilaterally in the dorsal part of the medial superior olive; contralateral to the injection in the dorsal parts of the intermediate and ventral nuclei of the lateral lemniscus; and in the anterolateral part of the central nucleus of the inferior colliculus. After an injection of [3H]-leucine in a posterior part of the anteroventral cochlear nucleus, presumably in a region sensitive to high frequencies, labeling is in the same set of nuclei, but within each nucleus the label is now in a different location: medially in the lateral superior olive, ventrally in the medial superior olive, ventrally in each division of the ventral and intermediate nuclei of the lateral lemniscus, and medially in the central nucleus of the inferior colliculus. Projections from the entire anteroventral cochlear nucleus to the inferior colliculus are confined to the ventral two-thirds of the central nucleus. The dorsal one-third of the central nucleus of the inferior colliculus is the principal target of the dorsal cochlear nucleus and may be a target of the posteroventral cochlear nucleus. Both of these nuclei appear to project sparsely to the ventral parts of the inferior colliculus. We conclude first that the bilateral input to the medial superior olive in the mustache bat is similar to the input seen in other mammals. Thus this bat has a neural structure which is associated with the analysis of binaural time differences and which usually is seen only in animals with heads large enough to create interaural time differences greater than those available to Pteronotus.(ABSTRACT TRUNCATED AT 400 WORDS)