Binaural Brainstem Research Articles

Novel standardized indexes of brainstem auditory evoked potentials for predicting hearing preservation in vestibular schwannomas

Hearing preservation (HP) during vestibular schwannomas (VSs) surgery poses a significant challenge. Although brainstem auditory evoked potentials (BAEPs) on the affected side are commonly employed to monitor cochlear nerve function, their low signal-to-noise ratio (SNR) renders them susceptible to interferences, compromising their reliability. We retrospectively analyzed the data of patients who underwent tumor resection, while binaural brainstem auditory evoked potentials (BAEPs) were simultaneously recorded during surgery. To standardize BAEPs on the affected side, we incorporated the synchronous healthy side as a reference (interval between affected and healthy side ≤ 3 min). A total of 127 patients were enrolled. Comparison of the raw BAEPs data pre- and post-tumor resection revealed that neither V-wave amplitude (Am-V) nor latency (La-V) could serve as reliable predictors of HP simultaneously. However, following standardization, V-wave latency (STIAS-La-V) and amplitude (STIAS-Am-V) emerged as stable predictors of HP. Furthermore, the intraoperative difference in V-wave amplitude (D-Am-V) predicted postoperative HP in patients with preoperative HP and remained predictive after standardization. The utilization of intraoperative synchronous healthy side BAEPs as a reference to eliminate interferences proves to be an effective approach in enhancing the reliability of BAEPs for predicting HP in VSs patients.

Binaural brainstem and spatial hearing deficits in a guinea pig model of noise-Induced cochlear synaptopathy

Animal studies have revealed that moderate-level noise exposure can cause a permanent loss of ribbon synapses between inner hair cells and auditory-nerve fibers, but only temporary threshold shifts. Such noise-induced cochlear synaptopathy has been called ‘hidden hearing loss’ because while there is a significant degeneration of ribbon synapses, the resulting hearing dysfunction is effectively hidden from typical clinical assays. Here we used guinea pigs to study the mechanisms leading to hearing deficits resulting from a moderate noise. We measured distortion product otoacoustic emissions and auditory brainstem responses to assay peripheral hearing. We tested spatial hearing ability through the prepulse inhibition (PPI) of the acoustic startle reflex. PPI was used to measure hearing-in-noise ability, or spatial release from masking, as this task approximates the “cocktail party” effect. Finally, we performed immunohistochemistry to confirm synaptopathy. Results show that the noise exposure induces no permanent hearing threshold shift, but despite recovery of normal audibility, both behavioral and electrophysiological binaural hearing deficits persisted. Cochlear synaptopathy was objectively confirmed by visualizing the loss of ribbon synapses in the cochlea. The results demonstrate that cochlear synaptopathy causes deficits in brainstem circuits known to be critical for binaural and spatial hearing. [Work supported by Otolaryngology T32 DC012280.]

Interaural Place-of-Stimulation Mismatch Estimates Using CT Scans and Binaural Perception, But Not Pitch, Are Consistent in Cochlear-Implant Users.

Bilateral cochlear implants (BI-CIs) or a CI for single-sided deafness (SSD-CI; one normally functioning acoustic ear) can partially restore spatial-hearing abilities, including sound localization and speech understanding in noise. For these populations, however, interaural place-of-stimulation mismatch can occur and thus diminish binaural sensitivity that relies on interaurally frequency-matched neurons. This study examined whether plasticity-reorganization of central neural pathways over time-can compensate for peripheral interaural place mismatch. We hypothesized differential plasticity across two systems: none for binaural processing but adaptation for pitch perception toward frequencies delivered by the specific electrodes. Interaural place mismatch was evaluated in 19 BI-CI and 23 SSD-CI human subjects (both sexes) using binaural processing (interaural-time-difference discrimination with simultaneous bilateral stimulation), pitch perception (pitch ranking for single electrodes or acoustic tones with sequential bilateral stimulation), and physical electrode-location estimates from computed-tomography (CT) scans. On average, CT scans revealed relatively little BI-CI interaural place mismatch (26° insertion-angle mismatch) but a relatively large SSD-CI mismatch, particularly at low frequencies (166° for an electrode tuned to 300 Hz, decreasing to 14° at 7000 Hz). For BI-CI subjects, the three metrics were in agreement because there was little mismatch. For SSD-CI subjects, binaural and CT measurements were in agreement, suggesting little binaural-system plasticity induced by mismatch. The pitch measurements disagreed with binaural and CT measurements, suggesting place-pitch plasticity or a procedural bias. These results suggest that reducing interaural place mismatch and potentially improving binaural processing by reprogramming the CI frequency allocation would be better done using CT-scan than pitch information.SIGNIFICANCE STATEMENT Electrode-array placement for cochlear implants (bionic prostheses that partially restore hearing) does not explicitly align neural representations of frequency information. The resulting interaural place-of-stimulation mismatch can diminish spatial-hearing abilities. In this study, adults with two cochlear implants showed reasonable interaural alignment, whereas those with one cochlear implant but normal hearing in the other ear often showed mismatch. In cases of mismatch, binaural sensitivity was best when the same cochlear locations were stimulated in both ears, suggesting that binaural brainstem pathways do not experience plasticity to compensate for mismatch. In contrast, interaurally pitch-matched electrodes deviated from cochlear-location estimates and did not optimize binaural sensitivity. Clinical correction of interaural place mismatch using binaural or computed-tomography (but not pitch) information may improve spatial-hearing benefits.

Normative Study of the Binaural Interaction Component of the Human Auditory Brainstem Response as a Function of Interaural Time Differences.

The binaural interaction component (BIC) of the auditory brainstem response (ABR) is obtained by subtracting the sum of the monaural right and left ear ABRs from the binaurally evoked ABR. The result is a small but prominent negative peak (herein called "DN1"), indicating a smaller binaural than summed ABR, which occurs around the latency of wave V or its roll-off slope. The BIC has been proposed to have diagnostic value as a biomarker of binaural processing abilities; however, there have been conflicting reports regarding the reliability of BIC measures in human subjects. The objectives of the current study were to: (1) examine prevalence of BIC across a large group of normal-hearing young adults; (2) determine effects of interaural time differences (ITDs) on BIC; and (3) examine any relationship between BIC and behavioral ITD discrimination acuity. Subjects were 40 normal-hearing adults (20 males and 20 females), aged 21 to 48 years, with no history of otologic or neurologic disorders. Midline ABRs were recorded from electrodes at high forehead (Fz) referenced to the nape of the neck (near the seventh cervical vertebra), with Fpz (low forehead) as the ground. ABRs were also recorded with a conventional earlobe reference for comparison to midline results. Stimuli were 90 dB peSPL biphasic clicks. For BIC measurements, stimuli were presented in a block as interleaved right monaural, left monaural, and binaural stimuli with 2000+ presentations per condition. Four measurements were averaged for a total of 8000+ stimuli per analyzed waveform. BIC was measured for ITD = 0 (simultaneous bilateral) and for ITDs of ±500 and ±750 µs. Subjects separately performed a lateralization task, using the same stimuli, to determine ITD discrimination thresholds. An identifiable BIC DN1 was obtained in 39 of 40 subjects at ITD = 0 µs in at least one of two measurement sessions, but was seen in lesser numbers of subjects in a single session or as ITD increased. BIC was most often seen when a subject was relaxed or sleeping, and less often when they fidgeted or reported neck tension, suggesting myogenic activity as a possible factor in disrupting BIC measurements. Mean BIC latencies systematically increased with increasing ITD, and mean BIC amplitudes tended to decrease. However, across subjects, there was no significant relationship between the amplitude or latency of the BIC and behavioral ITD thresholds. Consistent with previous studies, measurement of the BIC was time consuming and a BIC was sometimes difficult to obtain in awake normal-hearing subjects. The BIC will thus continue to be of limited clinical utility unless stimulus parameters and measurement techniques can be identified that produce a more robust response. Nonetheless, modulation of BIC characteristics by ITD supports the concept that the ABR BIC indexes aspects of binaural brainstem processing and thus may prove useful in selected research applications, e.g. in the examination of populations expected to have aberrant binaural signal processing ability.

Signatures of Somatic Inhibition and Dendritic Excitation in Auditory Brainstem Field Potentials.

Extracellular voltage recordings (Ve ; field potentials) provide an accessible view of in vivo neural activity, but proper interpretation of field potentials is a long-standing challenge. Computational modeling can aid in identifying neural generators of field potentials. In the auditory brainstem of cats, spatial patterns of sound-evoked Ve can resemble, strikingly, Ve generated by current dipoles. Previously, we developed a biophysically-based model of a binaural brainstem nucleus, the medial superior olive (MSO), that accounts qualitatively for observed dipole-like Ve patterns in sustained responses to monaural tones with frequencies >∼1000 Hz (Goldwyn et al., 2014). We have observed, however, that Ve patterns in cats of both sexes appear more monopole-like for lower-frequency tones. Here, we enhance our theory to accurately reproduce dipole and non-dipole features of Ve responses to monaural tones with frequencies ranging from 600 to 1800 Hz. By applying our model to data, we estimate time courses of paired input currents to MSO neurons. We interpret these inputs as dendrite-targeting excitation and soma-targeting inhibition (the latter contributes non-dipole-like features to Ve responses). Aspects of inferred inputs are consistent with synaptic inputs to MSO neurons including the tendencies of inhibitory inputs to attenuate in response to high-frequency tones and to precede excitatory inputs. Importantly, our updated theory can be tested experimentally by blocking synaptic inputs. MSO neurons perform a critical role in sound localization and binaural hearing. By solving an inverse problem to uncover synaptic inputs from Ve patterns we provide a new perspective on MSO physiology.SIGNIFICANCE STATEMENT Extracellular voltages (field potentials) are a common measure of brain activity. Ideally, one could infer from these data the activity of neurons and synapses that generate field potentials, but this "inverse problem" is not easily solved. We study brainstem field potentials in the region of the medial superior olive (MSO); a critical center in the auditory pathway. These field potentials exhibit distinctive spatial and temporal patterns in response to pure tone sounds. We use mathematical modeling in combination with physiological and anatomical knowledge of MSO neurons to plausibly explain how dendrite-targeting excitation and soma-targeting inhibition generate these field potentials. Inferring putative synaptic currents from field potentials advances our ability to study neural processing of sound in the MSO.

Auditory Model-Based Sound Direction Estimation With Bilateral Cochlear Implants.

Users of bilateral cochlear implants (CIs) show above-chance performance in localizing the source of a sound in the azimuthal (horizontal) plane; although localization errors are far worse than for normal-hearing listeners, they are considerably better than for CI listeners with only one implant. In most previous studies, subjects had access to interaural level differences and to interaural time differences conveyed in the temporal envelope. Here, we present a binaural model that predicts the azimuthal direction of sound arrival from a two-channel input signal as it is received at the left and right CI processor. The model includes a replication of a clinical speech-coding strategy, a model of the electrode-nerve interface and binaural brainstem neurons, and three different prediction stages that are trained to map the neural response rate to an azimuthal angle. The model is trained and tested with various noise and speech stimuli created by means of virtual acoustics. Localization error patterns of the model match experimental data and are explicable largely in terms of the nonmonotonic relationship between interaural level difference and azimuthal angle.

Intense and specialized dendritic localization of the fragile X mental retardation protein in binaural brainstem neurons: A comparative study in the alligator, chicken, gerbil, and human

Neuronal dendrites are structurally and functionally dynamic in response to changes in afferent activity. The fragile X mental retardation protein (FMRP) is an mRNA binding protein that regulates activity-dependent protein synthesis and morphological dynamics of dendrites. Loss and abnormal expression of FMRP occur in fragile X syndrome (FXS) and some forms of autism spectrum disorders. To provide further understanding of how FMRP signaling regulates dendritic dynamics, we examined dendritic expression and localization of FMRP in the reptilian and avian nucleus laminaris (NL) and its mammalian analogue, the medial superior olive (MSO), in rodents and humans. NL/MSO neurons are specialized for temporal processing of low-frequency sounds for binaural hearing, which is impaired in FXS. Protein BLAST analyses first demonstrate that the FMRP amino acid sequences in the alligator and chicken are highly similar to human FMRP with identical mRNA-binding and phosphorylation sites, suggesting that FMRP functions similarly across vertebrates. Immunocytochemistry further reveals that NL/MSO neurons have very high levels of dendritic FMRP in low-frequency hearing vertebrates including alligator, chicken, gerbil, and human. Remarkably, dendritic FMRP in NL/MSO neurons often accumulates at branch points and enlarged distal tips, loci known to be critical for branch-specific dendritic arbor dynamics. These observations support an important role for FMRP in regulating dendritic properties of binaural neurons that are essential for low-frequency sound localization and auditory scene segregation, and support the relevance of studying this regulation in nonhuman vertebrates that use low frequencies in order to further understand human auditory processing disorders.

Experimental Evidence for a Cochlear Source of the Precedence Effect

The precedence effect (PE) refers to the dominance of directional information carried by a direct sound (lead) over the spatial information contained in its multiple reflections (lags) in sound localization. Although the processes underlying the PE have been largely investigated, the extent to which peripheral versus central auditory processes contribute to this perceptual phenomenon has remained unclear. The present study investigated the contribution of peripheral processing to the PE through a comparison of physiological and psychoacoustical data in the same human listeners. The psychoacoustical experiments, comprising a fusion task, an interaural time difference detection task and a lateralization task, demonstrated a time range from 1 to 4.6–5 ms, in which the PE operated (precedence window). Click-evoked otoacoustic emissions (CEOAEs) were recorded in both ears to investigate the lead–lag interactions at the level of the basilar membrane (BM) in the cochlea. The CEOAE-derived peripheral and monaural lag suppression was largest for ICIs of 1–4 ms. Auditory-evoked brainstem responses (ABRs) were used to investigate monaural and binaural lag suppression at the brainstem level. The responses to monaural stimulation reflected the peripheral lag suppression observed in the CEOAE results, while the binaural brainstem responses did not show any substantial contribution of binaural processes to monaural lag suppression. The results demonstrated that the lag suppression occurring at the BM in a time range from 1 to 4 ms, as indicated by the suppression of the lag-CEOAE, was the source of the reduction in the lag-ABRs and a possible peripheral contributor to the PE for click stimuli.

Psychophysical and Physiological Evidence for Fast Binaural Processing

The mammalian auditory system is the temporally most precise sensory modality: To localize low-frequency sounds in space, the binaural system can resolve time differences between the ears with microsecond precision. In contrast, the binaural system appears sluggish in tracking changing interaural time differences as they arise from a low-frequency sound source moving along the horizontal plane. For a combined psychophysical and electrophysiological approach, we created a binaural stimulus, called "Phasewarp," that can transmit rapid changes in interaural timing. Using this stimulus, the binaural performance in humans is significantly better than reported previously and comparable with the monaural performance revealed with amplitude-modulated stimuli. Parallel, electrophysiological recordings of binaural brainstem neurons in the gerbil show fast temporal processing of monaural and different types of binaural modulations. In a refined electrophysiological approach that was matched to the psychophysics, the seemingly faster binaural processing of the Phasewarp was confirmed. The current data provide both psychophysical and physiological evidence against a general, hard-wired binaural sluggishness and reconcile previous contradictions of electrophysiological and psychophysical estimates of temporal binaural performance.

Effects of omni-directional noise-exposure during hearing onset and age on auditory spatial resolution in the Mongolian gerbil ( Meriones unguiculatus) — a behavioral approach

Inhibitory inputs to the binaural brainstem nuclei medial and lateral superior olives (MSO and LSO, respectively) are thought to be important for sound localization in mammals. Here, we investigate whether aged gerbils that typically exhibit degenerative changes in auditory nuclei providing inhibition to MSO and LSO show diminished localization ability. We also tested the localization ability in gerbils reared in omni-directional white noise during hearing onset, a treatment that affects the adjustment of inhibitory inputs to MSO neurons possibly resulting in weakened sensitivity to interaural time difference. Localization ability of both groups was compared to that of young gerbils raised under control conditions. Stimuli had a duration of 125 ms and were pure tones of 0.5, 1, 2, 4 and 8 kHz, 300-Hz-bands of noise centered at 0.5, 2 and 8 kHz or broad-band noise. Gerbils trained in a two-alternative-forced-choice procedure indicated if sounds were presented from the left or from the right by choosing the respective response compartment of a Y-shaped experimental setup. The minimum resolvable angle (MRA) was calculated as the minimum angle between two loudspeaker locations that a gerbil was able to discriminate. MRAs for aged gerbils were higher compared to controls, whereas MRAs of noise-reared gerbils did not differ from those of the control group. Results are discussed with respect to the progressive degeneration affecting the gerbil's auditory system, changes in the anatomical arrangement of inhibitory inputs on binaural neurons in the MSO, and hearing thresholds.

Abnormal Timing Delays in Auditory Brainstem Responses Evoked by Bilateral Cochlear Implant Use in Children

A period of unilateral implant use before bilateral implantation affects timing of brainstem processes measured by the electrically evoked auditory brainstem response (EABR). EABR latencies decrease with unilateral implant use potentially disrupting binaural timing cues important in auditory brainstem processing of bilateral input. EABRs were evoked by electrical pulses from the left, right, and both implants simultaneously in 3 groups of children. All were initially implanted at ages younger than 3 years and had the following: 1) a long delay (>2 yr [n = 16]), 2) a short delay (<1 yr [n = 15]), or 3) no delay (n = 15) between left and right ear implantation. Responses were recorded on the first day of bilateral implant use and 3 and 9 months thereafter. Relative to responses evoked in the experienced ear, the naive ear showed prolonged latency in both the EABR peaks and the binaural difference response. After 3 and 9 months of bilateral implant use, the relative prolongation decreased in the long and short delay groups, but significant differences persisted in the former. No clear differences in latencies evoked by the left versus right implant were found at any time point in children receiving bilateral implants simultaneously. Results suggest potential disruptions to binaural brainstem processing based on timing cues in children receiving a second cochlear implant after more than 2 years of unilateral implant use that persist through at least the first 9 months of bilateral implant use.

Spiking Neurons Learning Phase Delays: How Mammals May Develop Auditory Time-Difference Sensitivity

Time differences between the two ears are an important cue for animals to azimuthally locate a sound source. The first binaural brainstem nucleus, in mammals the medial superior olive, is generally believed to perform the necessary computations. Its cells are sensitive to variations of interaural time differences of about 10 micros. The classical explanation of such a neuronal time-difference tuning is based on the physical concept of delay lines. Recent data, however, are inconsistent with a temporal delay and rather favor a phase delay. By means of a biophysical model we show how spike-timing-dependent synaptic learning explains precise interplay of excitation and inhibition and, hence, accounts for a physical realization of a phase delay.

Synaptic plasticity determines the character of interaural-time-difference representation

Neuronal activity of cells in the first binaural brainstem nucleus, in mammals the MSO, depends on interaural time differences (ITDs). The neurons thereby resolve disparities of about 10 μs . Based on a computational model for the development of synaptic couplings, we give restrictions for a recently proposed coding hypothesis based on a monotonic dependence of the firing rate upon the ITD. We find that synaptic plasticity at MSO neurons with high best frequencies favors a rate-place code with a high variability of the tuning curves, as in the classical Jeffress model, whereas low best frequencies give rise to monotonic ITD dependence.

Encoding of sound motion by binaural brainstem units in a Horseshoe bat.

In order to study how and if single brainstem units respond to moving compared with stationary sounds, radially moving sound sources were presented to the bat, Rhinolophus ferrumequinum. This time-variant binaural stimulation was simulated dichotically through earphones (closed-acoustic-field for the virtual azimuth range of +/-40 degrees from the midline). Neurophysiologically recorded responses primarily showed a function of interaural intensity difference (IID) which is considered a direct correlate of the sound source's azimuth angle. However, this is only true for the stationary case. Unit's response did not remain unaffected by the dynamic stimulus cues of sound source movement (velocity and direction). Maximal discharge rate became a function of motion velocity as well as the slopes of the response profiles. Hence, coding of IID became ambiguous as, depending on the unit, the response profiles and therefore a unit's receptive field, became spatially shifted with respect to one another when the direction of the sound source movement was reversed. Shifts within the movement direction (hysteresis) as well as against it (termed here 'advance') were observed: hysteresis is typical for units with non-monotonic, stationary rate/intensity functions, whereas those units with monotonic functions predominantly show advances. Further dynamic response features in form of transient peaks and troughs, superimposed on the response profiles, were registered. It appears that the ongoing firing rate no longer represents azimuth position alone, but vigorously reproduces the dynamic cues (velocity and movement direction), too. With respect to the neural mechanisms leading to dynamic response features, it is proposed that, as long excitation and inhibition act with similar short time constants, neural activity can rapidly and faithfully follow changing IIDs. Different time constants for excitation, inhibition, facilitation, and depression may be responsible for the dynamic 'features' such as transient responses and hysteresis/advance. They may provide biologically relevant information for nocturnally hunting bats to efficiently guide their flight maneuvers.

Binaural response characteristics in isofrequency sheets of the gerbil inferior colliculus

The spatial distribution of neurons with different binaural response properties was studied in two isofrequency areas of the inferior colliculus (IC) of the gerbil ( Meriones unguiculatus). Single units were recorded in dorsomedial-to-ventrolaterally oriented electrode penetrations at different rostrocaudal positions, within a low (1–2 kHz; N = 108) and a high (23–27 kHz; N = 90) ‘iso-frequency’ sheet. Response types were not equally represented within the two layers. Within low-frequency regions, 41% of the units were excited following sound stimulation of either ear (EE), 21% received an excitatory input from one and an inhibitory input from the other ear (EI), and 12% were monaural (E0), while within high-frequency regions the distribution was 20% EE, 47% EI and 18% E0. However, the spatial arrangement of EE, EI and E0, within the dorsomedial-to-ventrolateral extent of the isofrequency sheets, was on the whole comparable within the two regions: EE-units were accumulated dorsomedially and EI-units ventrolaterally in the respective isofrequency sheets. E0-units were distributed equally within the low-frequency sheet but occurred more frequently in the middle part of the high-frequency lamina. About equal proportions of the units (low frequencies 9%; high frequencies 7%) had complex binaural response characteristics and were characterized as E/IE. In the rostrocaudal dimension of the nucleus, orderly arrangement of different unit types was less obvious. The results show that there is a tendency for grouping of different binaural unit types within the inferior colliculus. However, these unit types are not strictly segregated. Furthermore, it was shown that, despite the differences found in low- and high-frequency sites, there is a common scheme of ‘binaural representation’ across frequencies within the IC. Provided that EE-, EI-, and monaural response characteristics originate from separate sources, the data point to a convergence of binaural brainstem afferents within the IC.

Rate and frequency effects on brain stem binaural interaction responses

Spectrum and presentation rate were parameters utilized to evaluate the binaural interaction component (BIC) of the auditory brain stem response (ABR) at 100 dB SPL in normal hearing adults. Binaural brain stem waveforms were similar in morphology to the sums of the monaurals. For stimulus conditions of this study, amplitudes of the binaural wave V were always smaller with shorter latencies (0.1–0.2 ms) than the summed monaural amplitudes and latencies. Increasing stimulus rate produced small increases in response latencies and decreases in peak amplitudes of the N1‐P2 binaural interaction components and concomitantly, an increased latency and decreased amplitude of wave V of ABR. Rate effects at different center frequencies affected the BIC in ways significantly different from known effects of repetition rate on wave V ABR latencies using unfiltered clicks. Both the wave V of ABR and N1‐P2 component of BIC from all subjects consistently evoked shorter latencies to the 2000‐Hz tone bursts than to either 500‐ or 1000‐Hz tone bursts. At low frequencies, a derived frequency following response (FFR) was obtained having latencies and configurations which suggest that its emanation is central, not peripheral or artifactual.

Directional coding by binaural brainstem units of the CF-FM bat,Rhinolophus ferrumequinum

1. Monaural and binaural neurophysiological data were obtained from 264 units in the medullary and mesencephalic levels of the central auditory system in the CF-FM bat,Rhinolophus ferrumequinum, using earphones for acoustically separated stimulation of the two ears. 2. The units responded to pure tones delivered at their best frequencies with typical basic patterns (PST-histograms) which were classified according to the literature. 3. The latencies of the units' responses changed systematically with the recording depth from about 8 to 1.5ms when passing from the inferior colliculus at the brain's surface through the nucleus of the lateral lemniscus down to the superior olivary complex. 4. Best frequencies covered almost the whole hearing range from 2kHz up to 96kHz, but 50% of all units lay between 75 and 85kHz, the animal's best hearing range, the emission frequency of orientation sounds being between 82 and 84kHz (CF-part). 5. All lowest thresholds of single units put together demonstrate an almost perfect fitting with the behavioural hearing curve. 6. Monaural excitatory impulse count functions were mostly monotonic but many were very non-monotonic and intermediate. 7. The binaural classification (Table 1) confirmed the classical concept of the pathway and the theory of binaural interaction. The most frequently observed types were E/I (ipsilateral inhibitory, contralateral excitatory; 53 %) and E/E (both sides excitatory; 22%). 8. In all cases tested so far, best frequencies and tuning curves were the same for both sides regardless of the kind of binaural interaction. 9. The most interesting units found (13% of the total) showed together with binaural inhibition, strong facilitation in certain ranges of their dynamic range thus reinforcing the response to particular stimulus combinations. These units may be called directional specialists, useful for angular sensitivity. 10. The excitatory impulse count functions were usually steep covering a best dynamic range of 10–30dB, whereas inhibitory curves were much flatter but covered a wide dynamic range of 30–100dB. 11. Since therefore the excitatory influence is always predominant in any unit tested, coding of the sound direction is ambiguous when the absolute intensity is altered. Hence the response is not only a function of the interaural intensity difference as postulated by the theory, but also dependent upon absolute intensity levels. Neural mechanisms to compensate such ambiguities in presumably higher centers are postulated and discussed.

Some neural mechanisms in the inferior colliculus of the cat which may be relevant to localization of a sound source.

Some neural mechanisms in the inferior colliculus of the cat which may be relevant to localization of a sound source.