Transplantation of adipose-derived stromal cells protects functional and morphological auditory nerve integrity in a model of cochlear implantation.

Cochlear implants are considered the gold standard therapy for subjects with severe hearing loss and deafness. Cochlear implants bypass the damaged hair cells and directly stimulate spiral ganglion neurons (SGNs) of the auditory nerve. Hence, the presence of functional SGNs is crucial for speech perception in electric hearing with a cochlear implant. In deaf individuals, SGNs progressively degenerate due to the lack of neurotrophic support, normally provided by sensory cells of the inner ear. Adipose-derived stromal cells (ASCs) are known to produce neurotrophic factors. In a guinea pig model of sensory hearing loss and cochlear implantation, ASCs were autologously transplanted into the scala tympani prior to insertion of a cochlear implant on one side. Electrically evoked auditory brain stem responses (eABR) were recorded 8 weeks after cochlear implantation. At conclusion of the experiment, the cochleae were histologically evaluated. Compared to untreated control animals, transplantation of ASCs resulted in an increased number of SGNs and their peripheral neurites. In ASC-transplanted animals, mean eABR thresholds were lower and suprathreshold amplitudes larger, suggesting a larger population of intact auditory nerve fibers. Moreover, when compared to controls, amplitude-level functions of eABRs in ASC transplanted animals demonstrated steeper slopes in response to increasing interphase gaps (IPGs), indicative of better functionality of the auditory nerve. In summary, results suggest that transplantation of autologous ASCs into the deaf inner ear may have protective effects on the survival of SGNs and their peripheral processes and may thus contribute to long-term benefits in speech discrimination performance in cochlear implant subjects.

Neuroplastin expression is essential for hearing and hair cell PMCA expression.

Hearing deficits impact on the communication with the external world and severely compromise perception of the surrounding. Deafness can be caused by particular mutations in the neuroplastin (Nptn) gene, which encodes a transmembrane recognition molecule of the immunoglobulin (Ig) superfamily and plasma membrane Calcium ATPase (PMCA) accessory subunit. This study investigates whether the complete absence of neuroplastin or the loss of neuroplastin in the adult after normal development lead to hearing impairment in mice analyzed by behavioral, electrophysiological, and in vivo imaging measurements. Auditory brainstem recordings from adult neuroplastin-deficient mice (Nptn-/-) show that these mice are deaf. With age, hair cells and spiral ganglion cells degenerate in Nptn-/- mice. Adult Nptn-/- mice fail to behaviorally respond to white noise and show reduced baseline blood flow in the auditory cortex (AC) as revealed by single-photon emission computed tomography (SPECT). In adult Nptn-/- mice, tone-evoked cortical activity was not detectable within the primary auditory field (A1) of the AC, although we observed non-persistent tone-like evoked activities in electrophysiological recordings of some young Nptn-/- mice. Conditional ablation of neuroplastin in Nptnlox/loxEmx1Cre mice reveals that behavioral responses to simple tones or white noise do not require neuroplastin expression by central glutamatergic neurons. Loss of neuroplastin from hair cells in adult NptnΔlox/loxPrCreERT mice after normal development is correlated with increased hearing thresholds and only high prepulse intensities result in effective prepulse inhibition (PPI) of the startle response. Furthermore, we show that neuroplastin is required for the expression of PMCA 2 in outer hair cells. This suggests that altered Ca2+ homeostasis underlies the observed hearing impairments and leads to hair cell degeneration. Our results underline the importance of neuroplastin for the development and the maintenance of the auditory system.

Spectral plasticity in monkey primary auditory cortex limits performance generalization in a temporal discrimination task.

Auditory experience and behavioral training can modify perceptual performance. However, the consequences of temporal perceptual learning for temporal and spectral neural processing remain unclear. Specifically, the attributes of neural plasticity that underlie task generalization in behavioral performance remain uncertain. To assess the relationship between behavioral and neural plasticity, we evaluated neuronal temporal processing and spectral tuning in primary auditory cortex (AI) of anesthetized owl monkeys trained to discriminate increases in the envelope frequency (e.g., 4-Hz standard vs. >5-Hz targets) of sinusoidally amplitude-modulated (SAM) 1-kHz or 2-kHz carriers. Behavioral and neuronal performance generalization was evaluated for carriers ranging from 0.5 kHz to 8 kHz. Psychophysical thresholds revealed high SAM discrimination acuity for carriers from one octave below to ∼0.6 octave above the trained carrier frequency. However, generalization of SAM discrimination learning progressively declined for carrier frequencies >0.6 octave above the trained carrier frequency. Neural responses in AI showed that SAM discrimination training resulted in 1) increases in temporal modulation preference, especially at carriers close to the trained frequency, 2) narrowing of spectral tuning for neurons with characteristic frequencies near the trained carrier frequency, potentially limiting spectral generalization of temporal training effects, and 3) enhancement of firing-rate contrast for rewarded versus nonrewarded SAM frequencies, providing a potential cue for behavioral temporal discrimination near the trained carrier frequency. Our findings suggest that temporal training at a specific spectral location sharpens local frequency tuning, thus, confining the training effects to a narrow frequency range and limiting generalization of temporal discrimination learning across a wider frequency range.NEW & NOTEWORTHY Monkeys' ability to generalize amplitude modulation discrimination to nontrained carriers was limited to one octave below and 0.6 octave above the trained carrier frequency. Asymmetric generalization was paralleled by sharpening in cortical spectral tuning and enhanced firing-rate contrast between rewarded and nonrewarded SAM stimuli at carriers near the trained frequency. The spectral content of the training stimulus specified spectral and temporal plasticity that may provide a neural substrate for limitations in generalization of temporal discrimination learning.

Neural Processing of Acoustic and Electric Interaural Time Differences in Normal-Hearing Gerbils.

Bilateral cochlear implants (CIs) provide benefits for speech perception in noise and directional hearing, but users typically show poor sensitivity to interaural time differences (ITDs). Possible explanations for this deficit are deafness-induced degradations in neural ITD sensitivity, between-ear mismatches in electrode positions or activation sites, or differences in binaural brain circuits activated by electric versus acoustic stimulation. To identify potential limitations of electric ITD coding in the normal-hearing system, responses of single neurons in the dorsal nucleus of the lateral lemniscus and in the inferior colliculus to ITDs of electric (biphasic pulses) and acoustic (noise, clicks, chirps, and tones) stimuli were recorded in normal-hearing gerbils of either sex. To maintain acoustic sensitivity, electric stimuli were delivered to the round window. ITD tuning metrics (e.g., best ITD) and ITD discrimination thresholds for electric versus transient acoustic stimuli (clicks, chirps) obtained from the same neurons were not significantly correlated. Across populations of neurons with similar characteristic frequencies, however, ITD tuning metrics and ITD discrimination thresholds were similar for electric and acoustic stimuli and largely independent of the spectrotemporal properties of the acoustic stimuli when measured in the central range of ITDs. The similarity of acoustic and electric ITD coding on the population level in animals with normal hearing experience suggests that poorer ITD sensitivity in bilateral CI users compared with normal-hearing listeners is likely due to deprivation-induced changes in neural ITD coding rather than to differences in the binaural brain circuits involved in the processing of electric and acoustic ITDs.SIGNIFICANCE STATEMENT Small differences in the arrival time of sound at the two ears (interaural time differences, ITDs) provide important cues for speech understanding in noise and directional hearing. Deaf subjects with bilateral cochlear implants obtain only little benefit from ITDs. It is unclear whether these limitations are due to between-ear mismatches in activation sites, differences in binaural brain circuits activated by electric versus acoustic stimulation, or deafness-induced degradations in neural ITD processing. This study is the first to directly compare electric and acoustic ITD coding in neurons of known characteristic frequencies. In animals with normal hearing, populations of auditory brainstem and midbrain neurons demonstrate general similarities in electric and acoustic ITD coding, suggesting similar underlying central auditory processing mechanisms.

Adipose-derived stromal cells enhance auditory neuron survival in an animal model of sensory hearing loss.

BACKGROUND: A cochlear implant (CI) is an electronic prosthesis that can partially restore speech perception capabilities. Optimum information transfer from the cochlea to the central auditory system requires a proper functioning auditory nerve (AN) that is electrically stimulated by the device. In deafness, the lack of neurotrophic support, normally provided by the sensory cells of the inner ear, however, leads to gradual degeneration of auditory neurons with undesirable consequences for CI performance. METHODS: We evaluated the potential of adipose-derived stromal cells (ASCs) that are known to produce neurotrophic factors to prevent neural degeneration in sensory hearing loss. For this, co-cultures of ASCs with auditory neurons have been studied, and autologous ASC transplantation has been performed in a guinea pig model of gentamicin-induced sensory hearing loss. RESULTS: In vitro ASCs were neuroprotective and considerably increased the neuritogenesis of auditory neurons. In vivo transplantation of ASCs into the scala tympani resulted in an enhanced survival of auditory neurons. Specifically, peripheral AN processes that are assumed to be the optimal activation site for CI stimulation and that are particularly vulnerable to hair cell loss showed a significantly higher survival rate in ASC-treated ears. DISCUSSION/CONCLUSION: ASC transplantation into the inner ear may restore neurotrophic support in sensory hearing loss and may help to improve CI performance by enhanced AN survival.

Passive stimulation and behavioral training differentially transform temporal processing in the inferior colliculus and primary auditory cortex.

In profoundly deaf cats, behavioral training with intracochlear electric stimulation (ICES) can improve temporal processing in the primary auditory cortex (AI). To investigate whether similar effects are manifest in the auditory midbrain, ICES was initiated in neonatally deafened cats either during development after short durations of deafness (8 wk of age) or in adulthood after long durations of deafness (≥3.5 yr). All of these animals received behaviorally meaningless, "passive" ICES. Some animals also received behavioral training with ICES. Two long-deaf cats received no ICES prior to acute electrophysiological recording. After several months of passive ICES and behavioral training, animals were anesthetized, and neuronal responses to pulse trains of increasing rates were recorded in the central (ICC) and external (ICX) nuclei of the inferior colliculus. Neuronal temporal response patterns (repetition rate coding, minimum latencies, response precision) were compared with results from recordings made in the AI of the same animals (Beitel RE, Vollmer M, Raggio MW, Schreiner CE. J Neurophysiol 106: 944-959, 2011; Vollmer M, Beitel RE. J Neurophysiol 106: 2423-2436, 2011). Passive ICES in long-deaf cats remediated severely degraded temporal processing in the ICC and had no effects in the ICX. In contrast to observations in the AI, behaviorally relevant ICES had no effects on temporal processing in the ICC or ICX, with the single exception of shorter latencies in the ICC in short-deaf cats. The results suggest that independent of deafness duration passive stimulation and behavioral training differentially transform temporal processing in auditory midbrain and cortex, and primary auditory cortex emerges as a pivotal site for behaviorally driven neuronal temporal plasticity in the deaf cat. NEW & NOTEWORTHY: Behaviorally relevant vs. passive electric stimulation of the auditory nerve differentially affects neuronal temporal processing in the central nucleus of the inferior colliculus (ICC) and the primary auditory cortex (AI) in profoundly short-deaf and long-deaf cats. Temporal plasticity in the ICC depends on a critical amount of electric stimulation, independent of its behavioral relevance. In contrast, the AI emerges as a pivotal site for behaviorally driven neuronal temporal plasticity in the deaf auditory system.

Multichannel cochlear implant for selective neuronal activation and chronic use in the free-moving Mongolian gerbil.

BACKGROUND: Animal models for chronic multichannel cochlear implant stimulation and selective neuronal activation contribute to a better understanding of auditory signal processing and central neural plasticity. NEW METHOD: This paper describes the design and surgical implantation of a multichannel cochlear implant (CI) system for chronic use in the free-moving gerbil. For chronic stimulation, adult-deafened gerbils were connected to a multichannel commutator that allowed low resistance cable rotation and stable electric connectivity to the current source. RESULTS: Despite the small scale of the gerbil cochlea and auditory brain regions, final electrophysiological mapping experiments revealed selective and tonotopically organized neuronal activation in the auditory cortex. Contact impedances and electrically evoked auditory brainstem responses were stable over several weeks demonstrating the long-term integrity of the implant and the efficacy of the stimulation. COMPARISON WITH EXISTING METHODS: Most animal models on multichannel signal processing and stimulation-induced plasticity are limited to larger animals such as ferrets, cats and primates. Multichannel CI stimulation in the free-moving rodent and evidence for selective neuronal activation in gerbil auditory cortex have not been previously reported. CONCLUSIONS: Overall, our results show that the gerbil is a robust rodent model for selective and tonotopically organized multichannel CI stimulation. We anticipate that this model provides a useful tool to develop and test both passive stimulation and behavioral training strategies for plastic reorganization and restoration of degraded unilateral and bilateral central auditory signal processing in the hearing impaired and deaf central auditory system.

Modulation-frequency-specific adaptation in awake auditory cortex.

Amplitude modulations are fundamental features of natural signals, including human speech and nonhuman primate vocalizations. Because natural signals frequently occur in the context of other competing signals, we used a forward-masking paradigm to investigate how the modulation context of a prior signal affects cortical responses to subsequent modulated sounds. Psychophysical "modulation masking," in which the presentation of a modulated "masker" signal elevates the threshold for detecting the modulation of a subsequent stimulus, has been interpreted as evidence of a central modulation filterbank and modeled accordingly. Whether cortical modulation tuning is compatible with such models remains unknown. By recording responses to pairs of sinusoidally amplitude modulated (SAM) tones in the auditory cortex of awake squirrel monkeys, we show that the prior presentation of the SAM masker elicited persistent and tuned suppression of the firing rate to subsequent SAM signals. Population averages of these effects are compatible with adaptation in broadly tuned modulation channels. In contrast, modulation context had little effect on the synchrony of the cortical representation of the second SAM stimuli and the tuning of such effects did not match that observed for firing rate. Our results suggest that, although the temporal representation of modulated signals is more robust to changes in stimulus context than representations based on average firing rate, this representation is not fully exploited and psychophysical modulation masking more closely mirrors physiological rate suppression and that rate tuning for a given stimulus feature in a given neuron's signal pathway appears sufficient to engender context-sensitive cortical adaptation.

Spectral context affects temporal processing in awake auditory cortex.

Amplitude modulation encoding is critical for human speech perception and complex sound processing in general. The modulation transfer function (MTF) is a staple of auditory psychophysics, and has been shown to predict speech intelligibility performance in a range of adverse listening conditions and hearing impairments, including cochlear implant-supported hearing. Although both tonal and broadband carriers have been used in psychophysical studies of modulation detection and discrimination, relatively little is known about differences in the cortical representation of such signals. We obtained MTFs in response to sinusoidal amplitude modulation (SAM) for both narrowband tonal carriers and two-octave bandwidth noise carriers in the auditory core of awake squirrel monkeys. MTFs spanning modulation frequencies from 4 to 512 Hz were obtained using 16 channel linear recording arrays sampling across all cortical laminae. Carrier frequency for tonal SAM and center frequency for noise SAM was set at the estimated BF for each penetration. Changes in carrier type affected both rate and temporal MTFs in many neurons. Using spike discrimination techniques, we found that discrimination of modulation frequency was significantly better for tonal SAM than for noise SAM, though the differences were modest at the population level. Moreover, spike trains elicited by tonal and noise SAM could be readily discriminated in most cases. Collectively, our results reveal remarkable sensitivity to the spectral content of modulated signals, and indicate substantial interdependence between temporal and spectral processing in neurons of the core auditory cortex.

Behavioral training restores temporal processing in auditory cortex of long-deaf cats.

Temporal auditory processing is poor in prelingually hearing-impaired patients fitted with cochlear prostheses as adults. In an animal model of prelingual long-term deafness, we investigated the effects of behavioral training on temporal processing in the adult primary auditory cortex (AI). Neuronal responses to pulse trains of increasing frequencies were recorded in three groups of neonatally deafened cats that received a cochlear prosthesis after >3 yr of deafness: 1) acutely implanted animals that received no electric stimulation before study, 2) animals that received chronic-passive stimulation for several weeks to months before study, and 3) animals that received chronic-passive stimulation and additional behavioral training (signal detection). A fourth group of normal adult cats that was deafened acutely and implanted served as controls. The neuronal temporal response parameters of interest included the stimulus rate that evoked the maximum number of phase-locked spikes [best repetition rate (BRR)], the stimulus rate that produced 50% of the spike count at BRR (cutoff rate), the peak-response latency, and the first spike latency and timing-jitter. All long-deaf animals demonstrated a severe reduction in spiral ganglion cell density (mean, <6% of normal). Long-term deafness resulted in a significantly reduced temporal following capacity and spike-timing precision of cortical neurons in all parameters tested. Neurons in deaf animals that received only chronic-passive stimulation showed a gain in BRR but otherwise were similar to deaf cats that received no stimulation. In contrast, training with behaviorally relevant stimulation significantly enhanced all temporal processing parameters to normal levels with the exception of minimum latencies. These results demonstrate the high efficacy of learning-based remodeling of fundamental timing properties in cortical processing even in the adult, long-deaf auditory system, suggesting rehabilitative strategies for patients with long-term hearing loss.

Behavioral training enhances cortical temporal processing in neonatally deafened juvenile cats.

Deaf humans implanted with a cochlear prosthesis depend largely on temporal cues for speech recognition because spectral information processing is severely impaired. Training with a cochlear prosthesis is typically required before speech perception shows improvement, suggesting that relevant experience modifies temporal processing in the central auditory system. We tested this hypothesis in neonatally deafened cats by comparing temporal processing in the primary auditory cortex (AI) of cats that received only chronic passive intracochlear electric stimulation (ICES) with cats that were also trained with ICES to detect temporally challenging trains of electric pulses. After months of chronic passive stimulation and several weeks of detection training in behaviorally trained cats, multineuronal AI responses evoked by temporally modulated ICES were recorded in anesthetized animals. The stimulus repetition rates that produced the maximum number of phase-locked spikes (best repetition rate) and 50% cutoff rate were significantly higher in behaviorally trained cats than the corresponding rates in cats that received only chronic passive ICES. Behavioral training restored neuronal temporal following ability to levels comparable with those recorded in naïve prior normal-hearing adult deafened animals. Importantly, best repetitition rates and cutoff rates were highest for neuronal clusters activated by the electrode configuration used in behavioral training. These results suggest that neuroplasticity in the AI is induced by behavioral training and perceptual learning in animals deprived of ordinary auditory experience during development and indicate that behavioral training can ameliorate or restore temporal processing in the AI of profoundly deaf animals.

Neuronal responses in cat inferior colliculus to combined acoustic and electric stimulation.

The present study explored the interactions of combined electric and acoustic stimulation (EAS) on neural responses in the central auditory system. Normal-hearing cats were implanted unilaterally with scala tympani electrodes. Two experimental approaches were used. First, in a forward-masking paradigm, single biphasic electric pulses were used as maskers, unmodulated acoustic tone bursts at the neuron's characteristic frequency (CF) were used as probes. Then, in a simultaneous-masking paradigm, the masking effects of acoustic tones (CF) on responses to single electric pulses (probes) were examined. In the second approach, we studied the effects of phase relationship between acoustic and electric stimulation. Sinusoidal amplitude-modulated (30 Hz) CF tones and electric sinusoids (30 Hz) were shifted in relative phase (0-270 degrees). For all experimental conditions, the levels of the two stimuli were changed systematically. Responses were recorded in the contralateral central nucleus of the inferior colliculus. Single neuron analyses of spike rate and thresholds demonstrated that combined EAS resulted in complex interactions that were strongly dependent on the relative level of the given stimulus modes. The amount of masking increased with masker level and decreased with probe level. At higher current levels, the masking effect of electric responses dominated the effect of acoustic responses. The degree of these general masking effects was highly influenced by the relative phase between the combined stimuli. It seems likely that such interactions of combined stimulation have perceptual consequences in human cochlear implant subjects with residual hearing.

Spatial selectivity to intracochlear electrical stimulation in the inferior colliculus is degraded after long-term deafness in cats.

In an animal model of electrical hearing in prelingually deaf adults, this study examined the effects of deafness duration on response thresholds and spatial selectivity (i.e., cochleotopic organization, spatial tuning and dynamic range) in the central auditory system to intracochlear electrical stimulation. Electrically evoked auditory brain stem response (EABR) thresholds and neural response thresholds in the external (ICX) and central (ICC) nuclei of the inferior colliculus were estimated in cats after varying durations of neonatally induced deafness: in animals deafened <1.5 yr (short-deafened unstimulated, SDU cats) with a mean spiral ganglion cell (SGC) density of approximately 45% of normal and in animals deafened >2.5 yr (long-deafened, LD cats) with severe cochlear pathology (mean SGC density <7% of normal). LD animals were subdivided into unstimulated cats and those that received chronic intracochlear electrical stimulation via a feline cochlear implant. Acutely deafened, implanted adult cats served as controls. Independent of their stimulation history, LD animals had significantly higher EABR and ICC thresholds than SDU and control animals. Moreover, the spread of electrical excitation was significantly broader and the dynamic range significantly reduced in LD animals. Despite the prolonged durations of deafness the fundamental cochleotopic organization was maintained in both the ICX and the ICC of LD animals. There was no difference between SDU and control cats in any of the response properties tested. These findings suggest that long-term auditory deprivation results in a significant and possibly irreversible degradation of response thresholds and spatial selectivity to intracochlear electrical stimulation in the auditory midbrain.

Neurotrophic effects of GM1 ganglioside and electrical stimulation on cochlear spiral ganglion neurons in cats deafened as neonates.

Previous studies have shown that electrical stimulation of the cochlea by a cochlear implant promotes increased survival of spiral ganglion (SG) neurons in animals deafened early in life (Leake et al. [1999] J Comp Neurol 412:543-562). However, electrical stimulation only partially prevents SG degeneration after deafening and other neurotrophic agents that may be used along with an implant are of great interest. GM1 ganglioside is a glycosphingolipid that has been reported to be beneficial in treating stroke, spinal cord injuries, and Alzheimer's disease. GM1 activates trkB signaling and potentiates neurotrophins, and exogenous administration of GM1 has been shown to reduce SG degeneration after hearing loss. In the present study, animals were deafened as neonates and received daily injections of GM1, beginning either at birth or after animals were deafened and continuing until the time of cochlear implantation. GM1-treated and deafened control groups were examined at 7-8 weeks of age; additional GM1 and no-GM1 deafened control groups received a cochlear implant at 7-8 weeks of age and at least 6 months of unilateral electrical stimulation. Electrical stimulation elicited a significant trophic effect in both the GM1 group and the no-GM1 group as compared to the contralateral, nonstimulated ears. The results also demonstrated a modest initial improvement in SG density with GM1 treatment, which was maintained by and additive with the trophic effect of subsequent electrical stimulation. However, in the deafened ears contralateral to the implant SG soma size was severely reduced several months after withdrawal of GM1 in the absence of electrical activation.

Degradation of temporal resolution in the auditory midbrain after prolonged deafness is reversed by electrical stimulation of the cochlea.

In an animal model of prelingual deafness, we examined the anatomical and physiological effects of prolonged deafness and chronic electrical stimulation on temporal resolution in the adult central auditory system. Maximum following frequencies (Fmax) and first spike latencies of single neurons responding to electrical pulse trains were evaluated in the inferior colliculus of two groups of neonatally deafened cats after prolonged periods of deafness (>2.5 yr): the first group was implanted with an intracochlear electrode and studied acutely (long-deafened unstimulated, LDU); the second group (LDS) received a chronic implant and several weeks of electrical stimulation (pulse rates > or =300 pps). Acutely deafened and implanted adult cats served as controls. Spiral ganglion cell density in all long-deafened animals was markedly reduced (mean <5.8% of normal). Both long-term deafness and chronic electrical stimulation altered temporal resolution of neurons in the central nucleus (ICC) but not in the external nucleus. Specifically, LDU animals exhibited significantly poorer temporal resolution of ICC neurons (lower Fmax, longer response latencies) as compared with control animals. In contrast, chronic stimulation in LDS animals led to a significant increase in temporal resolution. Changes in temporal resolution after long-term deafness and chronic stimulation occurred broadly across the entire ICC and were not correlated with its tonotopic gradient. These results indicate that chronic electrical stimulation can reverse the degradation in temporal resolution in the auditory midbrain after long-term deafness and suggest the importance of factors other than peripheral pathology on plastic changes in the temporal processing capabilities of the central auditory system.

The effects of chronic intracochlear electrical stimulation on inferior colliculus spatial representation in adult deafened cats.

Previous studies have shown that chronic electrical stimulation through a cochlear implant causes significant alterations in the central auditory system of neonatally deafened cats. The goal of this study was to investigate the effects of chronic stimulation in the mature auditory system. Normal hearing adult animals were deafened by ototoxic drugs and received daily electrical stimulation over periods of 4-6 months. In terminal physiology experiments, response thresholds to pulsatile and sinusoidal signals were recorded within the inferior colliculus (IC). Using previously established methods, spatial tuning curves (STCs; threshold vs. IC depth functions) were constructed, and their widths measured to infer spatial selectivity. The IC spatial representations were similar for pulsatile and sinusoidal stimulation when phase duration was taken into consideration. However, sinusoidal signals consistently elicited much lower thresholds than pulsatile signals, a difference not solely attributable to differences in charge/phase. The average STC width was significantly broader in the adult deafened/stimulated animals than in controls (adult deafened/unstimulated cats), suggesting that electrical stimulation can induce spatial expansion of the IC representation of the chronically stimulated cochlear sector. Further, results in these adult animals were not significantly different from results in neonatally deafened, early stimulated animals, suggesting that a similar degree of plasticity was induced within the auditory midbrains of mature animals.