Monopolar intracochlear pulse trains selectively activate the inferior colliculus.

Previous cochlear implant studies using isolated electrical stimulus pulses in animal models have reported that intracochlear monopolar stimulus configurations elicit broad extents of neuronal activation within the central auditory system-much broader than the activation patterns produced by bipolar electrode pairs or acoustic tones. However, psychophysical and speech reception studies that use sustained pulse trains do not show clear performance differences for monopolar versus bipolar configurations. To test whether monopolar intracochlear stimulation can produce selective activation of the inferior colliculus, we measured activation widths along the tonotopic axis of the inferior colliculus for acoustic tones and 1,000-pulse/s electrical pulse trains in guinea pigs and cats. Electrical pulse trains were presented using an array of 6-12 stimulating electrodes distributed longitudinally on a space-filling silicone carrier positioned in the scala tympani of the cochlea. We found that for monopolar, bipolar, and acoustic stimuli, activation widths were significantly narrower for sustained responses than for the transient response to the stimulus onset. Furthermore, monopolar and bipolar stimuli elicited similar activation widths when compared at stimulus levels that produced similar peak spike rates. Surprisingly, we found that in guinea pigs, monopolar and bipolar stimuli produced narrower sustained activation than 60 dB sound pressure level acoustic tones when compared at stimulus levels that produced similar peak spike rates. Therefore, we conclude that intracochlear electrical stimulation using monopolar pulse trains can produce activation patterns that are at least as selective as bipolar or acoustic stimulation.

Microelectrode arrays fabricated using a novel hybrid microfabrication method.

We present novel hybrid microfabrication methods for microelectrode arrays that combine microwire assembly, microelectromechanical systems (MEMS) manufacturing techniques and precision tool-based micromachining. This combination enables hybrid microfabrication to produce complex geometries and structures, increase material selection, and improve integration. A 32-channel shank microelectrode array was fabricated to highlight the hybrid microfabrication techniques. The electrode shank was 130 µm at its narrowest, had a 127 µm thickness and had iridium oxide electrode sites that were 25 µm in diameter with 150 µm spacing. Techniques used to fabricate this electrode include microassembly of insulated gold wires into a micromold, micromolding the microelectrode shank, post molding machining, sacrificial release of the microelectrode and electrodeposition of iridium oxide onto the microelectrode sites. Electrode site position accuracy was shown to have a standard deviation of less than 4 µm. Acute in vivo recordings with the 32-channel shank microelectrode array demonstrated comparable performance to that obtained with commercial microelectrode arrays. This new approach to microelectrode array fabrication will enable new microelectrodes, such as multi-sided arrays, drug eluding electrodes and biodegradable shanks.

Selective electrical stimulation of the auditory nerve activates a pathway specialized for high temporal acuity.

Deaf people who use cochlear implants show surprisingly poor sensitivity to the temporal fine structure of sounds. One possible reason is that conventional cochlear implants cannot activate selectively the auditory-nerve fibers having low characteristic frequencies (CFs), which, in normal hearing, phase lock to stimulus fine structure. Recently, we tested in animals an alternative mode of auditory prosthesis using penetrating auditory-nerve electrodes that permit frequency-specific excitation in all frequency regions. We present here measures of temporal transmission through the auditory brainstem, from pulse trains presented with various auditory-nerve electrodes to phase-locked activity of neurons in the central nucleus of the inferior colliculus (ICC). On average, intraneural stimulation resulted in significant ICC phase locking at higher pulse rates (i.e., higher "limiting rates") than did cochlear-implant stimulation. That could be attributed, however, to the larger percentage of low-CF neurons activated selectively by intraneural stimulation. Most ICC neurons with limiting rates >500 pulses per second had CFs <1.5 kHz, whereas neurons with lower limiting rates tended to have higher CFs. High limiting rates also correlated strongly with short first-spike latencies. It follows that short latencies correlated significantly with low CFs, opposite to the correlation observed with acoustical stimulation. These electrical-stimulation results reveal a high-temporal-acuity brainstem pathway characterized by low CFs, short latencies, and high-fidelity transmission of periodic stimulation. Frequency-specific stimulation of that pathway by intraneural stimulation might improve temporal acuity in human users of a future auditory prosthesis, which in turn might improve musical pitch perception and speech reception in noise.

Retuning of inferior colliculus neurons following spiral ganglion lesions: a single-neuron model of converging inputs.

Lesions of spiral ganglion cells, representing a restricted sector of the auditory nerve array, produce immediate changes in the frequency tuning of inferior colliculus (IC) neurons. There is a loss of excitation at the lesion frequencies, yet responses to adjacent frequencies remain intact and new regions of activity appear. This leads to immediate changes in tuning and in tonotopic progression. Similar effects are seen after different methods of peripheral damage and in auditory neurons in other nuclei. The mechanisms that underlie these postlesion changes are unknown, but the acute effects seen in IC strongly suggest the "unmasking" of latent inputs by the removal of inhibition. In this study, we explore computational models of single neurons with a convergence of excitatory and inhibitory inputs from a range of characteristic frequencies (CFs), which can simulate the narrow prelesion tuning of IC neurons, and account for the changes in CF tuning after a lesion. The models can reproduce the data if inputs are aligned relative to one another in a precise order along the dendrites of model IC neurons. Frequency tuning in these neurons approximates that seen physiologically. Removal of inputs representing a narrow range of frequencies leads to unmasking of previously subthreshold excitatory inputs, which causes changes in CF. Conversely, if all of the inputs converge at the same point on the cell body, receptive fields are broad and unmasking rarely results in CF changes. However, if the inhibition is tonic with no stimulus-driven component, then unmasking can still produce changes in CF.

Acute changes in frequency responses of inferior colliculus central nucleus (ICC) neurons following progressively enlarged restricted spiral ganglion lesions.

Immediate effects of sequential and progressively enlarged spiral ganglion (SG) lesions were recorded from cochleas and inferior colliculi. Small SG-lesions produced modest elevations in cochlear tone-evoked compound action potential (CAP) thresholds across narrow frequency ranges; progressively enlarged lesions produced progressively higher CAP-threshold elevations across progressively wider frequency ranges. No comparable changes in distortion product otoacoustic emissions (DPOAEs) amplitudes were observed consistent with silencing of auditory nerve sectors without affecting organ of Corti function. Frequency response areas (FRAs) of inferior colliculus (IC) neurons were recorded before and immediately after SG-lesions using multi-site silicon arrays fixed in place with recording sites arrayed along IC frequency gradient. Individual post-lesion FRAs exhibited progressively elevated response thresholds and diminished response amplitudes at lesion frequencies, whereas responses at non-lesion frequencies were either unchanged or enhanced. Characteristic frequencies were shifted and silent areas were introduced within these FRAs. Sequentially larger lesions produced sequentially larger shifts in CF and/or enlarged silent areas within affected FRAs, producing immediate changes in IC frequency organization. These results contrast with those from the auditory nerve, extend previous reports of experience-induced plasticity in the auditory CNS, and support results indicating afferent convergence onto ICC neurons across broad frequency bands.

Effects of age at onset of deafness and electrical stimulation on the developing cochlear nucleus in cats.

This study examined the effects of deafness and intracochlear electrical stimulation on the anatomy of the cochlear nucleus (CN) after a brief period of normal auditory development early in life. Kittens were deafened by systemic ototoxic drug injections either as neonates or starting at postnatal day 30. Total CN volume, individual CN subdivision volumes, and cross-sectional areas of spherical cell somata in the anteroventral CN (AVCN) were compared in neonatally deafened and 30-day deafened groups at 8 weeks of age and in young adults after approximately 6 months of electrical stimulation initiated at 8 weeks of age. Both neonatal and early acquired hearing loss resulted in a reduction in CN volume as compared to normal hearing cats. Comparison of 8- and 32-week old groups indicated that the CN continued to grow in both deafened groups despite the absence of auditory input. Preserving normal auditory input for 30 days resulted in a significant increase in both total CN volume and cross-sectional areas of spherical cell somata, as compared to neonatally deafened animals. Restoring auditory input in these developing animals by unilateral intracochlear electrical stimulation did not elicit any difference in CN volume between the two sides, but resulted in 7% larger spherical cell size on the stimulated side. Overall, the brief period of normal auditory development and subsequent electrical stimulation maintained CN volume at 80% of normal and spherical cell size at 86% of normal ipsilateral to the implant as compared to 67% and 74%, respectively, in the neonatally deafened group.

Topography of auditory nerve projections to the cochlear nucleus in cats after neonatal deafness and electrical stimulation by a cochlear implant.

We previously reported that auditory nerve projections from the cochlear spiral ganglion (SG) to the cochlear nucleus (CN) exhibit clear cochleotopic organization in adult cats deafened as neonates before hearing onset. However, the topographic specificity of these CN projections in deafened animals is proportionately broader than normal (less precise relative to the CN frequency gradient). This study examined SG-to-CN projections in adult cats that were deafened as neonates and received a unilateral cochlear implant at approximately 7 weeks of age. Following several months of electrical stimulation, SG projections from the stimulated cochleae were compared to projections from contralateral, non-implanted ears. The fundamental organization of SG projections into frequency band laminae was clearly evident, and discrete projections were always observed following double SG injections in deafened cochleae, despite severe auditory deprivation and/or broad electrical activation of the SG. However, when normalized for the smaller CN size after deafness, AVCN, PVCN, and DCN projections on the stimulated side were broader by 32%, 34%, and 53%, respectively, than projections in normal animals (although absolute projection widths were comparable to normal). Further, there was no significant difference between projections from stimulated and contralateral non-implanted cochleae. These findings suggest that early normal auditory experience may be essential for normal development and/or maintenance of the topographic precision of SG-to-CN projections. After early deafness, the CN is smaller than normal, the topographic distribution of these neural projections that underlie frequency resolution in the central auditory system is proportionately broader, and projections from adjacent SG sectors are more overlapping. Several months of stimulation by a cochlear implant (beginning at approximately 7 weeks of age) did not lessen or exacerbate these degenerative changes observed in adulthood. One clinical implication of these findings is that congenitally deaf cochlear implant recipients may have central auditory system alterations that limit their ability to achieve spectral selectivity equivalent to post-lingually deafened subjects.

Intraneural stimulation for auditory prosthesis: modiolar trunk and intracranial stimulation sites.

We have demonstrated recently in an animal model that stimulation with a penetrating auditory nerve electrode array is a feasible means of activating the ascending auditory pathway for auditory prosthesis. Compared to a conventional intrascalar cochlear implant, intraneural stimulation provides access to fibers serving a broader frequency range, activation of more tonotopically restricted fiber populations, lower thresholds, and reduced interference between simultaneously stimulated channels. The spread of excitation by a single intraneural electrode is broader than that by an acoustic tone but narrower than that by a cochlear-implant electrode. In the present study, we compare in an animal model two sites of intraneural stimulation: the modiolar trunk of the nerve accessed using a transcochlear approach and the intracranial portion of the nerve accessed using a posterior fossa approach. The two stimulation sites offer very similar thresholds, spread of activation, and dynamic ranges. The intracranial site differed in that there was greater between-animal variation in tonotopic patterns. We discuss the implications of these results for possible improvements in hearing prosthesis for human subjects.

Cochlear implant electrode configuration effects on activation threshold and tonotopic selectivity.

The multichannel design of contemporary cochlear implants (CIs) is predicated on the assumption that each channel activates a relatively restricted and independent sector of the deaf auditory nerve array, just as a sound within a restricted frequency band activates a restricted region of the normal cochlea The independence of CI channels, however, is limited; and the factors that determine their independence, the relative overlap of the activity patterns that they evoke, are poorly understood. In this study, we evaluate the spread of activity evoked by cochlear implant channels by monitoring activity at 16 sites along the tonotopic axis of the guinea pig inferior colliculus (IC). "Spatial tuning curves" (STCs) measured in this way serve as an estimate of activation spread within the cochlea and the ascending auditory pathways. We contrast natural stimulation using acoustic tones with two kinds of electrical stimulation either (1) a loose fitting banded array consisting of a cylindrical silicone elastomer carrier with a linear series of ring contacts; or (2) a space-filling array consisting of a tapered silicone elastomer carrier that is designed to fit snugly into the guinea pig scala tympani with a linear series of ball contacts positioned along it Spatial tuning curves evoked by individual acoustic tones, and by activation of each contact of each array as a monopole, bipole or tripole were recorded. Several channel configurations and a wide range of electrode separations were tested for each array, and their thresholds and selectivity were estimated. The results indicate that the tapered space-filling arrays evoked more restricted activity patterns at lower thresholds than did the banded arrays. Monopolar stimulation (one intracochlear contact activated with an extracochlear return) using either array evoked broad activation patterns that involved the entire recording array at current levels <6dBSL, but at relatively low thresholds. Bi- and tri-polar configurations of both array types evoked more restricted activity patterns, but their thresholds were higher than those of monopolar configurations. Bipolar and tripolar configurations with closely spaced contacts evoked activity patterns that were comparable to those evoked by pure tones. As the spacing of bipolar electrodes was increased (separations >1mm), the activity patterns became broader and evoked patterns with two distinct threshold minima, one associated with each contact.

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.

Spontaneous discharge patterns in cochlear spiral ganglion cells before the onset of hearing in cats.

Spontaneous neural activity has been recorded in the auditory nerve of cats as early as 2 days postnatal (P2), yet individual auditory neurons do not respond to ambient sound levels <90-100 dB SPL until about P10. Significant refinement of the central projections from the spiral ganglion to the cochlear nucleus occurs during this neonatal period. This refinement may be dependent on peripheral spontaneous discharge activity. We recorded from single spiral ganglion cells in kittens aged P3-P9. The spiral ganglion was accessed through the round window through the spiral lamina. A total of 112 ganglion cells were isolated for study in nine animals. Spike rates in neonates were very low, ranging from 0.06 to 56 spikes/s, with a mean of 3.09 +/- 8.24 spikes/s. Ganglion cells in neonatal kittens exhibited remarkable repetitive spontaneous bursting discharge patterns. The unusual patterns were evident in the large mean interval CV (CV(i) = 2.9 +/- 1.6) and burst index of 5.2 +/- 3.5 across ganglion cells. Spontaneous bursting patterns in these neonatal mammals were similar to those reported for cochlear ganglion cells of the embryonic chicken, suggesting this may be a general phenomenon that is common across animal classes. Rhythmic spontaneous discharge of retinal ganglion cells has been shown to be important in the development of central retinotopic projections and normal binocular vision. Bursting rhythms in cochlear ganglion cells may play a similar role in the auditory system during prehearing periods.

Design and fabrication of multichannel cochlear implants for animal research.

The effectiveness of multichannel cochlear implants depends on the activation of perceptually distinct regions of the auditory nerve. Increased information transfer is possible as the number of channels and dynamic range are increased and electrical and neural interaction among channels is reduced. Human and animal studies have demonstrated that specific design features of the intracochlear electrode directly affect these performance factors. These features include the geometry, size, and orientation of the stimulating sites, proximity of the device to spiral ganglion neurons, shape and position of the insulating carrier, and the stimulation mode (monopolar, bipolar, etc.). Animal studies to directly measure the effects of changes in electrode design are currently constrained by the lack of available electrodes that model contemporary clinical devices. This report presents methods to design and fabricate species-specific customizable electrode arrays. We have successfully implanted these arrays in guinea pigs and cats for periods of up to 14 months and have conducted acute electrophysiological experiments in these animals. Modifications enabling long-term intracochlear drug infusion are also described. Studies using these scale model arrays will improve our understanding of how these devices function in human subjects and how we can best optimize future cochlear implants.

Auditory prosthesis with a penetrating nerve array.

Contemporary auditory prostheses ("cochlear implants") employ arrays of stimulating electrodes implanted in the scala tympani of the cochlea. Such arrays have been implanted in some 100,000 profoundly or severely deaf people worldwide and arguably are the most successful of present-day neural prostheses. Nevertheless, most implant users show poor understanding of speech in noisy backgrounds, poor pitch recognition, and poor spatial hearing, even when using bilateral implants. Many of these limitations can be attributed to the remote location of stimulating electrodes relative to excitable cochlear neural elements. That is, a scala tympani electrode array lies within a bony compartment filled with electrically conductive fluid. Moreover, scala tympani arrays typically do not extend to the apical turn of the cochlea in which low frequencies are represented. In the present study, we have tested in an animal model an alternative to the conventional cochlear implant: a multielectrode array implanted directly into the auditory nerve. We monitored the specificity of stimulation of the auditory pathway by recording extracellular unit activity at 32 sites along the tonotopic axis of the inferior colliculus. The results demonstrate the activation of specific auditory nerve populations throughout essentially the entire frequency range that is represented by characteristic frequencies in the inferior colliculus. Compared to conventional scala tympani stimulation, thresholds for neural excitation are as much as 50-fold lower and interference between electrodes stimulated simultaneously is markedly reduced. The results suggest that if an intraneural stimulating array were incorporated into an auditory prosthesis system for humans, it could offer substantial improvement in hearing replacement compared to contemporary cochlear implants.

Neonatal deafness results in degraded topographic specificity of auditory nerve projections to the cochlear nucleus in cats.

We previously examined the early postnatal maturation of the primary afferent auditory nerve projections from the cat cochlear spiral ganglion (SG) to the cochlear nucleus (CN). In normal kittens these projections exhibit clear cochleotopic organization before birth, but quantitative data showed that their topographic specificity is less precise in perinatal kittens than in adults. Normalized for CN size, projections to the anteroventral (AVCN), posteroventral (PVCN), and dorsal (DCN) subdivisions are all significantly broader in neonates than in adults. By 6-7 postnatal days, projections are proportionate to those of adults, suggesting that significant refinement occurs during the early postnatal period. The present study examined SG projections to the CN in adult cats deafened as neonates by ototoxic drug administration. The fundamental organization of the SG-to-CN projections into frequency band laminae is clearly evident despite severe auditory deprivation from birth. However, when normalized for the smaller CN size in deafened animals, projections are disproportionately broader than in controls; AVCN, PVCN, and DCN projections are 39, 26, and 48% broader, respectively, than predicted if they were precisely proportionate to projections in normal hearing animals. These findings suggest that normal auditory experience and neural activity are essential for the early postnatal development (or subsequent maintenance) of the topographic precision of SG-to-CN projections. After early deafness, the basic cochleotopic organization of the CN is established and maintained into adulthood, but the CN is severely reduced in size and the topographic specificity of primary afferent projections that underlies frequency resolution in the normal central auditory system is significantly degraded.

Cochlear implants: the view from the brain.

The cochlear implant arguably is the most successful neural prosthesis. Studies of the responses of the central auditory system to prosthetic electrical stimulation of the cochlea are revealing the success with which electrical stimulation of a deaf ear can mimic acoustic stimulation of a normal-hearing ear. Understanding of the physiology of central auditory structures can lead to improved restoration of hearing with cochlear implants. In turn, the cochlear implant can be exploited as an experimental tool for examining central hearing mechanisms isolated from the effects of cochlear mechanics and transduction.

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.

Topographic spread of inferior colliculus activation in response to acoustic and intracochlear electric stimulation.

The design of contemporary multichannel cochlear implants is predicated on the presumption that they activate multiple independent sectors of the auditory nerve array. The independence of these channels, however, is limited by the spread of activation from each intracochlear electrode across the auditory nerve array. In this study, we evaluated factors that influence intracochlear spread of activation using two types of intracochlear electrodes: (1) a clinical-type device consisting of a linear series of ring contacts positioned along a silicon elastomer carrier, and (2) a pair of visually placed (VP) ball electrodes that could be positioned independently relative to particular intracochlear structures, e.g., the spiral ganglion. Activation spread was estimated by recording multineuronal evoked activity along the cochleotopic axis of the central nucleus of the inferior colliculus (ICC). This activity was recorded using silicon-based single-shank, 16-site recording probes, which were fixed within the ICC at a depth defined by responses to acoustic tones. After deafening, electric stimuli consisting of single biphasic electric pulses were presented with each electrode type in various stimulation configurations (monopolar, bipolar, tripolar) and/or various electrode orientations (radial, off-radial, longitudinal). The results indicate that monopolar (MP) stimulation with either electrode type produced widepread excitation across the ICC. Bipolar (BP) stimulation with banded pairs of electrodes oriented longitudinally produced activation that was somewhat less broad than MP stimulation, and tripolar (TP) stimulation produced activation that was more restricted than MP or BP stimulation. Bipolar stimulation with radially oriented pairs of VP ball electrodes produced the most restricted activation. The activity patterns evoked by radial VP balls were comparable to those produced by pure tones in normal-hearing animals. Variations in distance between radially oriented VP balls had little effect on activation spread, although increases in interelectrode spacing tended to reduce thresholds. Bipolar stimulation with longitudinally oriented VP electrodes produced broad activation that tended to broaden as the separation between electrodes increased.

Postnatal refinement of auditory nerve projections to the cochlear nucleus in cats.

Studies of visual system development have suggested that competition driven by activity is essential for refinement of initial topographically diffuse neuronal projections into their precise adult patterns. This has led to the assertion that this process may shape development of topographic connections throughout the nervous system. Because the cat auditory system is very immature at birth, with auditory nerve neurons initially exhibiting very low or no spontaneous activity, we hypothesized that the auditory nerve fibers might initially form topographically broad projections within the cochlear nuclei (CN), which later would become topographically precise at the time when adult-like frequency selectivity develops. In this study, we made restricted injections of Neurobiotin, which labeled small sectors (300-500 microm) of the cochlear spiral ganglion, to study the projections of auditory nerve fibers representing a narrow band of frequencies. Results showed that projections from the basal cochlea to the CN are tonotopically organized in neonates, many days before the onset of functional hearing and even prior to the development of spontaneous activity in the auditory nerve. However, results also demonstrated that significant refinement of the topographic specificity of the primary afferent axons of the auditory nerve occurs in late gestation or early postnatal development. Projections to all three subdivisions of the CN exhibit clear tonotopic organization at or before birth, but the topographic restriction of fibers into frequency band laminae is significantly less precise in perinatal kittens than in adult cats. Two injections spaced > or = 2 mm apart in the cochlea resulted in labeled bands of projecting axons in the anteroventral CN that were 53% broader than would be expected if they were proportional to those in adults, and the two projections were incompletely segregated in the youngest animals studied. Posteroventral CN (PVCN) projections (normalized for CN size) were 36% broader in neonates than in adults, and projections from double injections in the youngest subjects were nearly fused in the PVCN. Projections to the dorsal division of the CN were 32% broader in neonates than in adults when normalized, but the dorsal CN projections were always discrete, even at the earliest ages studied.

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.

Immediate changes in tuning of inferior colliculus neurons following acute lesions of cat spiral ganglion.

In previous studies, we demonstrated that acute lesions the spiral ganglion (SG), the cells of origin of the auditory nerve (AN), change the frequency organization of the inferior colliculus central nucleus (ICC) and primary auditory cortex (AI). In those studies, we used a map/re-map approach and recorded the tonotopic organization of neurons before and after restricted SG lesions. In the present study, response areas (RAs) of ICC multi-neuronal clusters were recorded to contralateral and ipsilateral tones after inserting and fixing-in-place tungsten microelectrodes. RAs were recorded from most electrodes before, immediately (within 33-78 min) after, and long (several hours) after restricted mechanical lesions of the ganglion. Each SG lesion produced a "notch" in the tone-evoked compound action potential (CAP) audiogram corresponding to a narrow range of lesion frequencies with elevated thresholds. Responses of contralateral IC neurons, which responded to these lesion frequencies, underwent an elevation in threshold to the lesion frequencies with either no change in sensitivity to other frequencies or with dramatic decreases in threshold to lesion-edge frequencies. These changes in sensitivity produced shifts in characteristic frequency (CF) that could be more than an octave. Thresholds at these new CFs matched the prelesion thresholds of neurons tuned to the lesion-edge frequencies. Responses evoked by ipsilateral tones delivered to the intact ear often underwent complementary changes, i.e., decreased thresholds to lesion frequency tones with little or no change in sensitivity to other frequencies. These results indicate that responses of IC neurons are produced by convergence of auditory information across a wide range of AN fibers and that the acute "plastic" changes reported in our previous studies occur within 1 h of an SG lesion.