Exploring the Use of Interleaved Stimuli to Measure Cochlear-Implant Excitation Patterns.

PURPOSE: Attempts to use current-focussing strategies with cochlear implants (CI) to reduce neural spread-of-excitation have met with only mixed success in human studies, in contrast to promising results in animal studies. Although this discrepancy could stem from between-species anatomical and aetiological differences, the masking experiments used in human studies may be insufficiently sensitive to differences in excitation-pattern width. METHODS: We used an interleaved-masking method to measure psychophysical excitation patterns in seven participants with four masker stimulation configurations: monopolar (MP), partial tripolar (pTP), a wider partial tripolar (pTP + 2), and, importantly, a condition (RP + 2) designed to produce a broader excitation pattern than MP. The probe was always in partial-tripolar configuration. RESULTS: We found a significant effect of stimulation configuration on both the amount of on-site masking (mask and probe on same electrode; an indirect indicator of sharpness) and the difference between off-site and on-site masking. Differences were driven solely by RP + 2 producing a broader excitation pattern than the other configurations, whereas monopolar and the two current-focussing configurations did not statistically differ from each other. CONCLUSION: A method that is sensitive enough to reveal a modest broadening in RP + 2 showed no evidence for sharpening with focussed stimulation. We also showed that although voltage recordings from the implant accurately predicted a broadening of the psychophysical excitation patterns with RP + 2, they wrongly predicted a strong sharpening with pTP + 2. We additionally argue, based on our recent research, that the interleaved-masking method can usefully be applied to non-human species and objective measures of CI excitation patterns.

Artifact removal by template subtraction enables recordings of the frequency following response in cochlear-implant users.

Electrically evoked frequency-following responses (eFFRs) provide insight in the phase-locking ability of brainstem of cochlear-implant (CI) users. eFFRs can potentially be used to gain insight in the individual differences in the biological limitation on temporal encoding of the electrically stimulated auditory pathway, which can be inherent to the electrical stimulation itself and/or the degenerative processes associated with hearing loss. One of the major challenge of measuring eFFRs in CI users is the process of isolating the stimulation artifact from the neural response, as both the response and the artifact overlap in time and have similar frequency characteristics. Here we introduce a new artifact removal method based on template subtraction that successfully removes the stimulation artifacts from the recordings when CI users are stimulated with pulse trains from 128 to 300 pulses per second in a monopolar configuration. Our results show that, although artifact removal was successful in all CI users, the phase-locking ability of the brainstem to the different pulse rates, as assessed with the eFFR differed substantially across participants. These results show that the eFFR can be measured, free from artifacts, in CI users and that they can be used to gain insight in individual differences in temporal processing of the electrically stimulated auditory pathway.

High Spectral and Temporal Acuity in Primary Auditory Cortex of Awake Cats.

Most accounts of single- and multi-unit responses in auditory cortex under anesthetized conditions have emphasized V-shaped frequency tuning curves and low-pass sensitivity to rates of repeated sounds. In contrast, single-unit recordings in awake marmosets also show I-shaped and O-shaped response areas having restricted tuning to frequency and (for O units) sound level. That preparation also demonstrates synchrony to moderate click rates and representation of higher click rates by spike rates of non-synchronized tonic responses, neither of which are commonly seen in anesthetized conditions. The spectral and temporal representation observed in the marmoset might reflect special adaptations of that species, might be due to single- rather than multi-unit recording, or might indicate characteristics of awake-versus-anesthetized recording conditions. We studied spectral and temporal representation in the primary auditory cortex of alert cats. We observed V-, I-, and O-shaped response areas like those demonstrated in awake marmosets. Neurons could synchronize to click trains at rates about an octave higher than is usually seen with anesthesia. Representations of click rates by rates of non-synchronized tonic responses exhibited dynamic ranges that covered the entire range of tested click rates. The observation of these spectral and temporal representations in cats demonstrates that they are not unique to primates and, indeed, might be widespread among mammalian species. Moreover, we observed no significant difference in stimulus representation between single- and multi-unit recordings. It appears that the principal factor that has hindered observations of high spectral and temporal acuity in the auditory cortex has been the use of general anesthesia.

Informational Masking in Aging and Brain-lesioned Individuals.

Auditory stream segregation and informational masking were investigated in brain-lesioned individuals, age-matched controls with no neurological disease, and young college-age students. A psychophysical paradigm known as rhythmic masking release (RMR) was used to examine the ability of participants to identify a change in the rhythmic sequence of 20-ms Gaussian noise bursts presented through headphones and filtered through generalized head-related transfer functions to produce the percept of an externalized auditory image (i.e., a 3D virtual reality sound). The target rhythm was temporally interleaved with a masker sequence comprising similar noise bursts in a manner that resulted in a uniform sequence with no information remaining about the target rhythm when the target and masker were presented from the same location (an impossible task). Spatially separating the target and masker sequences allowed participants to determine if there was a change in the target rhythm midway during its presentation. RMR thresholds were defined as the minimum spatial separation between target and masker sequences that resulted in 70.7% correct-performance level in a single-interval 2-alternative forced-choice adaptive tracking procedure. The main findings were (1) significantly higher RMR thresholds for individuals with brain lesions (especially those with damage to parietal areas) and (2) a left-right spatial asymmetry in performance for lesion (but not control) participants. These findings contribute to a better understanding of spatiotemporal relations in informational masking and the neural bases of auditory scene analysis.

Electrophysiological and Psychophysical Measures of Temporal Pitch Sensitivity in Normal-hearing Listeners.

To obtain combined behavioural and electrophysiological measures of pitch perception, we presented harmonic complexes, bandpass filtered to contain only high-numbered harmonics, to normal-hearing listeners. These stimuli resemble bandlimited pulse trains and convey pitch using a purely temporal code. A core set of conditions consisted of six stimuli with baseline pulse rates of 94, 188 and 280 pps, filtered into a HIGH (3365-4755 Hz) or VHIGH (7800-10,800 Hz) region, alternating with a 36% higher pulse rate. Brainstem and cortical processing were measured using the frequency following response (FFR) and auditory change complex (ACC), respectively. Behavioural rate change difference limens (DLs) were measured by requiring participants to discriminate between a stimulus that changed rate twice (up-down or down-up) during its 750-ms presentation from a constant-rate pulse train. FFRs revealed robust brainstem phase locking whose amplitude decreased with increasing rate. Moderate-sized but reliable ACCs were obtained in response to changes in purely temporal pitch and, like the psychophysical DLs, did not depend consistently on the direction of rate change or on the pulse rate for baseline rates between 94 and 280 pps. ACCs were larger and DLs lower for stimuli in the HIGH than in the VHGH region. We argue that the ACC may be a useful surrogate for behavioural measures of rate discrimination, both for normal-hearing listeners and for cochlear-implant users. We also showed that rate DLs increased markedly when the baseline rate was reduced to 48 pps, and compared the behavioural and electrophysiological findings to recent cat data obtained with similar stimuli and methods.

Tonotopic Selectivity in Cats and Humans: Electrophysiology and Psychophysics.

We describe a scalp-recorded measure of tonotopic selectivity, the "cortical onset response" (COR) and compare the results between humans and cats. The COR results, in turn, were compared with psychophysical masked-detection thresholds obtained using similar stimuli and obtained from both species. The COR consisted of averaged responses elicited by 50-ms tone-burst probes presented at 1-s intervals against a continuous noise masker. The noise masker had a bandwidth of 1 or 1/8th octave, geometrically centred on 4000 Hz for humans and on 8000 Hz for cats. The probe frequency was either - 0.5, - 0.25, 0, 0.25 or 0.5 octaves re the masker centre frequency. The COR was larger for probe frequencies more distant from the centre frequency of the masker, and this effect was greater for the 1/8th-octave than for the 1-octave masker. This pattern broadly reflected the masked excitation patterns obtained psychophysically with similar stimuli in both species. However, the positive signal-to-noise ratio used to obtain reliable COR measures meant that some aspects of the data differed from those obtained psychophysically, in a way that could be partly explained by the upward spread of the probe's excitation pattern. Our psychophysical measurements also showed that the auditory filter width obtained at 8000 Hz using notched-noise maskers was slightly wider in cat than previous measures from humans. We argue that although conclusions from COR measures differ in some ways from conclusions based on psychophysics, the COR measures provide an objective, noninvasive, valid measure of tonotopic selectivity that does not require training and that may be applied to acoustic and cochlear-implant experiments in humans and laboratory animals.

Temporal Pitch Sensitivity in an Animal Model: Psychophysics and Scalp Recordings : Temporal Pitch Sensitivity in Cat.

Cochlear implant (CI) users show limited sensitivity to the temporal pitch conveyed by electric stimulation, contributing to impaired perception of music and of speech in noise. Neurophysiological studies in cats suggest that this limitation is due, in part, to poor transmission of the temporal fine structure (TFS) by the brainstem pathways that are activated by electrical cochlear stimulation. It remains unknown, however, how that neural limit might influence perception in the same animal model. For that reason, we developed non-invasive psychophysical and electrophysiological measures of temporal (i.e., non-spectral) pitch processing in the cat. Normal-hearing (NH) cats were presented with acoustic pulse trains consisting of band-limited harmonic complexes that simulated CI stimulation of the basal cochlea while removing cochlear place-of-excitation cues. In the psychophysical procedure, trained cats detected changes from a base pulse rate to a higher pulse rate. In the scalp-recording procedure, the cortical-evoked acoustic change complex (ACC) and brainstem-generated frequency following response (FFR) were recorded simultaneously in sedated cats for pulse trains that alternated between the base and higher rates. The range of perceptual sensitivity to temporal pitch broadly resembled that of humans but was shifted to somewhat higher rates. The ACC largely paralleled these perceptual patterns, validating its use as an objective measure of temporal pitch sensitivity. The phase-locked FFR, in contrast, showed strong brainstem encoding for all tested pulse rates. These measures demonstrate the cat's perceptual sensitivity to pitch in the absence of cochlear-place cues and may be valuable for evaluating neural mechanisms of temporal pitch perception in the feline animal model of stimulation by a CI or novel auditory prostheses.

A Search for a Cortical Map of Auditory Space.

This is the story of a search for a cortical map of auditory space. The search began with a study that was reported in the first issue of the Journal of Neuroscience (Middlebrooks and Pettigrew, 1981, 1:107-120.). That paper described some unexpected features of spatial sensitivity in the auditory cortex while failing to demonstrate the expected map. In the ensuing 40 years, we have encountered: panoramic spatial coding by single neurons; a rich variety of response patterns that are unmasked in the absence of general anesthesia; sharpening of spatial sensitivity when an animal is engaged in a listening task; and reorganization of spatial sensitivity in the presence of competing sounds. We have not encountered a map, but not through lack of trying. On the basis of years of negative results by our group and others, and positive results that are inconsistent with static point-to-point topography, we are confident in concluding that there just ain't no map. Instead, we have come to appreciate the highly dynamic spatial properties of cortical neurons, which serve the needs of listeners in a changing sonic environment.

Spatial Mechanisms for Segregation of Competing Sounds, and a Breakdown in Spatial Hearing.

We live in complex auditory environments, in which we are confronted with multiple competing sounds, including the cacophony of talkers in busy markets, classrooms, offices, etc. The purpose of this article is to synthesize observations from a series of experiments that focused on how spatial hearing might aid in disentangling interleaved sequences of sounds. The experiments were unified by a non-verbal task, "rhythmic masking release", which was applied to psychophysical studies in humans and cats and to cortical physiology in anesthetized cats. Human and feline listeners could segregate competing sequences of sounds from sources that were separated by as little as ∼10°. Similarly, single neurons in the cat primary auditory cortex tended to synchronize selectively to sound sequences from one of two competing sources, again with spatial resolution of ∼10°. The spatial resolution of spatial stream segregation varied widely depending on the binaural and monaural acoustical cues that were available in various experimental conditions. This is in contrast to a measure of basic sound-source localization, the minimum audible angle, which showed largely constant acuity across those conditions. The differential utilization of acoustical cues suggests that the central spatial mechanisms for stream segregation differ from those for sound localization. The highest-acuity spatial stream segregation was derived from interaural time and level differences. Brainstem processing of those cues is thought to rely heavily on normal function of a voltage-gated potassium channel, Kv3.3. A family was studied having a dominant negative mutation in the gene for that channel. Affected family members exhibited severe loss of sensitivity for interaural time and level differences, which almost certainly would degrade their ability to segregate competing sounds in real-world auditory scenes.

Design, Fabrication, and Evaluation of a Parylene Thin-Film Electrode Array for Cochlear Implants.

OBJECTIVE: To improve the existing manually assembled cochlear implant electrode arrays, a thin-film electrode array (TFEA) was microfabricated having a maximum electrode density of 15 sites along an 8-mm length, with each site having a 75 µm × 1.8 µm (diameter × height) disk electrode. METHODS: The microfabrication method adopted photoresist transferring, lift-off, two-step oxygen plasma etching, and fuming nitric acid release to reduce lift-off complexity, protect the metal layer, and increase the release efficiency. RESULTS: Systematic in vitro characterization showed that the TFEA's bending stiffness was 6.40 × 10-10 N·m2 near the base and 1.26 × 10-10 N·m2 near the apex. The TFEA electrode produced an average impedance of 16 kΩ and a maximum current limit of 800 µA, measured with 1-kHz sinusoidal current using monopolar stimulation in saline. A TFEA prototype was implanted in a cat cochlea to obtain in vivo measurements of electrically evoked auditory brainstem and inferior colliculus responses to monopolar stimulation with 41-µs/phase biphasic pulses. Both physiological responses produced a threshold of ∼300 µA and a dynamic range of 5-8 dB above the threshold. Compared with existing arrays, the present TFEA had 104 times less bending stiffness, 97% less electrode area, and comparable physiological thresholds. CONCLUSION: Using a simplified structure and stable fabrication method, the present TEFA produced physical and physiological performance comparable to existing commercial devices. SIGNIFICANCE: The present TFEA represents a step closer toward an automated process replacing the labor-intensive and expensive manual assembly of the cochlear implant electrode arrays.

Study of the Carrier-Aided Thin Film Electrode Array Design for Cochlear Insertion.

The micro-fabricated thin film electrode array (TFEA) has been a promising design for cochlear implants (CIs) because of its cost-effectiveness and fabrication precision. The latest polymer-based cochlear TFEAs have faced difficulties for cochlear insertion due to the lack of structural stiffness. To stiffen the TFEA, dissolvable stiffening materials, TFEAs with different structures, and TFEAs with commercial CIs as carriers have been invested. In this work, the concept of enhancing a Parylene TFEA with Kapton tape as a simpler carrier for cochlear insertion has been proved to be feasible. The bending stiffness of the Kapton-aided TFEA was characterized with an analytical model, a finite element model, and a cantilever bending experiment, respectively. While the Kapton tape increased the bending stiffness of the Parylene TFEA by 10³ times, the 6-µm-thick TFEA with a similar Young's modulus, as a polyimide, in turn significantly increased the bending stiffness of the 170-µm-thick Kapton carrier by 60%. This result indicated that even the TFEA is ultra-flexible and that its bending stiffness should not be neglected in the design or selection of its carrier.

Chronic Deafness Degrades Temporal Acuity in the Electrically Stimulated Auditory Pathway.

Electrical stimulation of the auditory nerve with a penetrating intraneural (IN) electrode in acutely deafened cats produces much more restricted spread of excitation than is obtained in that preparation with a conventional cochlear implant (CI) as reported by Middlebrooks and Snyder (J Assoc Res Otolaryngol 8:258-279, 2007). That suggests that a future auditory prosthesis employing IN stimulation might offer human patients greater frequency selectivity than is available with a present-day CI. Nevertheless, it is a concern that the electrical field produced by an IN electrode might be too restricted to produce adequate stimulation of the partially depopulated auditory nerve of a deaf patient. We evaluated this by testing responses to IN and CI stimulation in adult-deafened cats. Activation of the auditory pathway was monitored by recording from the central nucleus of the inferior colliculus (ICC). Cats deaf for 153-277 days exhibited a ~ 30 % loss of auditory nerve fibers compared to cats deaf for < 18 h. Contrary to our concern, measures of thresholds and dynamic ranges showed no significant deafness-related impairment of excitation by IN or CN stimulation. Surprisingly, however, temporal acuity decreased dramatically in these adult-deafened cats, as demonstrated by a marked decrease in the maximum rate of electrical cochlear stimulation to which ICC neurons synchronized to IN or CI stimulation. For instance, half of ICC neurons synchronized to IN stimulation up to 203 pulses per second (pps) in acute deafness, whereas that number dropped to 79 pps for chronic deafness. Such a loss of temporal acuity might contribute to the poor sensitivity to temporal fine structure that has been reported in human CI users. Seemingly, the degraded temporal acuity that we observed in cats was even worse than the fine-structure sensitivity of human CI users, suggesting that most patients experience some improvement of temporal acuity resulting from restoration of patterned auditory nerve stimulation by a CI.

Tone-Evoked Acoustic Change Complex (ACC) Recorded in a Sedated Animal Model.

The acoustic change complex (ACC) is a scalp-recorded cortical evoked potential complex generated in response to changes (e.g., frequency, amplitude) in an auditory stimulus. The ACC has been well studied in humans, but to our knowledge, no animal model has been evaluated. In particular, it was not known whether the ACC could be recorded under the conditions of sedation that likely would be necessary for recordings from animals. For that reason, we tested the feasibility of recording ACC from sedated cats in response to changes of frequency and amplitude of pure-tone stimuli. Cats were sedated with ketamine and acepromazine, and subdermal needle electrodes were used to record electroencephalographic (EEG) activity. Tones were presented from a small loudspeaker located near the right ear. Continuous tones alternated at 500-ms intervals between two frequencies or two levels. Neurometric functions were created by recording neural response amplitudes while systematically varying the magnitude of steps in frequency centered in octave frequency around 2, 4, 8, and 16 kHz, all at 75 dB SPL, or in decibel level around 75 dB SPL tested at 4 and 8 kHz. The ACC could be recorded readily under this ketamine/azepromazine sedation. In contrast, ACC could not be recorded reliably under any level of isoflurane anesthesia that was tested. The minimum frequency (expressed as Weber fractions (df/f)) or level steps (expressed in dB) needed to elicit ACC fell in the range of previous thresholds reported in animal psychophysical tests of discrimination. The success in recording ACC in sedated animals suggests that the ACC will be a useful tool for evaluation of other aspects of auditory acuity in normal hearing and, presumably, in electrical cochlear stimulation, especially for novel stimulation modes that are not yet feasible in humans.

Selective recurrent laryngeal nerve stimulation using a penetrating electrode array in the feline model.

OBJECTIVES/HYPOTHESIS: Laryngeal muscles (LMs) are controlled by the recurrent laryngeal nerve (RLN), injury of which can result in vocal fold (VF) paralysis (VFP). We aimed to introduce a bioelectric approach to selective stimulation of LMs and graded muscle contraction responses. STUDY DESIGN: Acute experiments in cats. METHODS: The study included six anesthetized cats. In four cats, a multichannel penetrating microelectrode array (MEA) was placed into an uninjured RLN. For RLN injury experiments, one cat received a standardized hemostat-crush injury, and one cat received a transection-reapproximation injury 4 months prior to testing. In each experiment, three LMs (thyroarytenoid, posterior cricoarytenoid, and cricothyroid muscles) were monitored with an electromyographic (EMG) nerve integrity monitoring system. Electrical current pulses were delivered to each stimulating channel individually. Elicited EMG voltage outputs were recorded for each muscle. Direct videolaryngoscopy was performed for visualization of VF movement. RESULTS: Stimulation through individual channels led to selective activation of restricted nerve populations, resulting in selective contraction of individual LMs. Increasing current levels resulted in rising EMG voltage responses. Typically, activation of individual muscles was successfully achieved via single placement of the MEA by selection of appropriate stimulation channels. VF abduction was predominantly observed on videolaryngoscopy. Nerve histology confirmed injury in cases of RLN crush and transection experiments. CONCLUSIONS: We demonstrated the ability of a penetrating MEA to selectively stimulate restricted fiber populations within the feline RLN and selectively elicit contractions of discrete LMs in both acute and injury-model experiments, suggesting a potential role for intraneural MEA implantation in VFP management. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:1606-1614, 2018.

Selective Stimulation of Facial Muscles Following Chronic Intraneural Electrode Array Implantation and Facial Nerve Injury in the Feline Model.

BACKGROUND: Our group has previously shown that activation of specific facial nerve (FN) fiber populations and selective activation of facial musculature can be achieved through acute intraneural multichannel microelectrode array (MEA) implantation in the feline model. HYPOTHESIS: Selective stimulation of facial muscles will be maintained in the setting of 1) chronic and 2) acute MEA implantation after FN injury and subsequent recovery. METHODS: This study included seven cats. In three cats with normal facial function, 4-channel penetrating MEAs were implanted chronically in the FN and tested biweekly for 6 months. Electrical current pulses were delivered to each channel individually, and elicited electromyographic (EMG) voltage outputs were recorded for each of several facial muscles. For FN injury experiments, two cats received a standardized hemostat-crush injury, and two cats received a transection-reapproximation injury to the FN main trunk. These four underwent acute implantation of MEA and EMG recording in terminal experiments 4 months postinjury. RESULTS: Stimulation through individual channels selectively activated restricted nerve populations, resulting in activation of individual muscles in cats with chronic MEA implantation and after nerve injury. Increasing stimulation current levels resulted in increasing EMG voltage responses in all patients. Nerve histology showed only minor neural tissue reaction to the implant. CONCLUSION: We have established in the animal model the ability of a chronically implanted MEA to selectively stimulate restricted FN fiber populations and elicit activations in specific facial muscles. Likewise, after FN injury, selective stimulation of restricted FN fiber populations and subsequent activation of discrete facial muscles can be achieved after acute MEA implantation.

Selective stimulation of facial muscles with a penetrating electrode array in the feline model.

OBJECTIVES/HYPOTHESIS: Permanent facial nerve injury is a difficult challenge for both patients and physicians given its potential for debilitating functional, cosmetic, and psychological sequelae. Although current surgical interventions have provided considerable advancements in facial nerve rehabilitation, they often fail to fully address all impairments. We aim to introduce an alternative approach to facial nerve rehabilitation. STUDY DESIGN: Acute experiments in animals with normal facial function. METHODS: The study included three anesthetized cats. Four facial muscles (levator auris longus, orbicularis oculi, nasalis, and orbicularis oris) were monitored with a standard electromyographic (EMG) facial nerve monitoring system with needle electrodes. The main trunk of the facial nerve was exposed, and a 16-channel penetrating electrode array was placed into the nerve. Electrical current pulses were delivered to each stimulating electrode individually. Elicited EMG voltage outputs were recorded for each muscle. RESULTS: Stimulation through individual channels selectively activated restricted nerve populations, resulting in selective contraction of individual muscles. Increasing stimulation current levels resulted in increasing EMG voltage responses. Typically, selective activation of two or more distinct muscles was successfully achieved via a single placement of the multi-channel electrode array by selection of appropriate stimulation channels. CONCLUSION: We have established in the animal model the ability of a penetrating electrode array to selectively stimulate restricted fiber populations within the facial nerve and to selectively elicit contractions in specific muscles and regions of the face. These results show promise for the development of a facial nerve implant system. LEVEL OF EVIDENCE: N/A.Laryngoscope, 2016 127:460-465, 2017.

Masking release by combined spatial and masker-fluctuation effects in the open sound field.

In a complex auditory scene, signals of interest can be distinguished from masking sounds by differences in source location [spatial release from masking (SRM)] and by differences between masker-alone and masker-plus-signal envelopes. This study investigated interactions between those factors in release of masking of 700-Hz tones in an open sound field. Signal and masker sources were colocated in front of the listener, or the signal source was shifted 90° to the side. In Experiment 1, the masker contained a 25-Hz-wide on-signal band plus flanking bands having envelopes that were either mutually uncorrelated or were comodulated. Comodulation masking release (CMR) was largely independent of signal location at a higher masker sound level, but at a lower level CMR was reduced for the lateral signal location. In Experiment 2, a brief signal was positioned at the envelope maximum (peak) or minimum (dip) of a 50-Hz-wide on-signal masker. Masking was released in dip more than in peak conditions only for the 90° signal. Overall, open-field SRM was greater in magnitude than binaural masking release reported in comparable closed-field studies, and envelope-related release was somewhat weaker. Mutual enhancement of masking release by spatial and envelope-related effects tended to increase with increasing masker level.

Spatial Stream Segregation by Cats.

Listeners can perceive interleaved sequences of sounds from two or more sources as segregated streams. In humans, physical separation of sound sources is a major factor enabling such stream segregation. Here, we examine spatial stream segregation with a psychophysical measure in domestic cats. Cats depressed a pedal to initiate a target sequence of brief sound bursts in a particular rhythm and then released the pedal when the rhythm changed. The target bursts were interleaved with a competing sequence of bursts that could differ in source location but otherwise were identical to the target bursts. This task was possible only when the sources were heard as segregated streams. When the sound bursts had broad spectra, cats could detect the rhythm change when target and competing sources were separated by as little as 9.4°. Essentially equal levels of performance were observed when frequencies were restricted to a high, 4-to-25-kHz, band in which the principal spatial cues presumably were related to sound levels. When the stimulus band was restricted from 0.4 to 1.6 kHz, leaving interaural time differences as the principal spatial cue, performance was severely degraded. The frequency sensitivity of cats in this task contrasts with that of humans, who show better spatial stream segregation with low- than with high-frequency sounds. Possible explanations for the species difference includes the smaller interaural delays available to cats due to smaller sizes of their heads and the potentially greater sound-level cues available due to the cat's frontally directed pinnae and higher audible frequency range.

Emergence of Spatial Stream Segregation in the Ascending Auditory Pathway.

Stream segregation enables a listener to disentangle multiple competing sequences of sounds. A recent study from our laboratory demonstrated that cortical neurons in anesthetized cats exhibit spatial stream segregation (SSS) by synchronizing preferentially to one of two sequences of noise bursts that alternate between two source locations. Here, we examine the emergence of SSS along the ascending auditory pathway. Extracellular recordings were made in anesthetized rats from the inferior colliculus (IC), the nucleus of the brachium of the IC (BIN), the medial geniculate body (MGB), and the primary auditory cortex (A1). Stimuli consisted of interleaved sequences of broadband noise bursts that alternated between two source locations. At stimulus presentation rates of 5 and 10 bursts per second, at which human listeners report robust SSS, neural SSS is weak in the central nucleus of the IC (ICC), it appears in the nucleus of the brachium of the IC (BIN) and in approximately two-thirds of neurons in the ventral MGB (MGBv), and is prominent throughout A1. The enhancement of SSS at the cortical level reflects both increased spatial sensitivity and increased forward suppression. We demonstrate that forward suppression in A1 does not result from synaptic inhibition at the cortical level. Instead, forward suppression might reflect synaptic depression in the thalamocortical projection. Together, our findings indicate that auditory streams are increasingly segregated along the ascending auditory pathway as distinct mutually synchronized neural populations. SIGNIFICANCE STATEMENT: Listeners are capable of disentangling multiple competing sequences of sounds that originate from distinct sources. This stream segregation is aided by differences in spatial location between the sources. A possible substrate of spatial stream segregation (SSS) has been described in the auditory cortex, but the mechanisms leading to those cortical responses are unknown. Here, we investigated SSS in three levels of the ascending auditory pathway with extracellular unit recordings in anesthetized rats. We found that neural SSS emerges within the ascending auditory pathway as a consequence of sharpening of spatial sensitivity and increasing forward suppression. Our results highlight brainstem mechanisms that culminate in SSS at the level of the auditory cortex.