Intracochlear Electrical Stimulation Research Articles

The history of cochlear implantation: from Volta to multichannel-intracochlear stimulation

Seit der Consensus Conference 1995 ist das Cochlear Implant (CI) als Methode der Wahl bei cochleäer Taubheit etabliert. Mit Hilfe des CI ist es erstmals möglich, den auditiven Sinneskanal nach dem Funktionsverlust des Perzeptionsorganes wieder zu nutzen. Weltweit tragen heute mehr als 30 000 Patienten ein CI. Mittlerweile erscheint es bereits selbstverständlich, die Therapie mit Innenohrimplantaten in das Spektrum der HNO-ärztlichen Behandlung als eine Standardtherapie einzubeziehen.

Transcription Factor Modulation and Expression in the Rat Auditory Brainstem Following Electrical Intracochlear Stimulation

Neuronal activity in sensory organs elicited by adequate or electrical stimulation not only invokes fast electrical responses but may also trigger complex molecular changes inside central neurons. Following electrical intracochlear stimulation with a cochlear implant under urethane anesthesia, we observed changes in the phosphorylation state of the cAMP response element binding protein (CREB) and the expression of the immediate-early genes c-fos and egr-1, molecules known to act as transcription factors, in a tonotopically precise pattern in central auditory neurons. These neurons resided in the posteroventral and anteroventral cochlear nucleus, the dorsal cochlear nucleus, the lateral superior olive, the medial nucleus of the trapezoid body, the dorsal and ventral nucleus of the lateral lemniscus, and the central nucleus of the inferior colliculus. Moreover, effects of electrical stimulation were identified in the medial vestibular nucleus and the lateral parabrachial nucleus. Regionally, CREB was dephosphorylated wherever immediate-early gene expression went up. These massive stimulation-dependent modulations of transcription factors in the ascending auditory system are indicative of ongoing changes that modify the chemistry and structure of the affected cells and, consequently, their response characteristics to subsequent stimulation of the inner ear.

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.

Cortical map plasticity in animals and humans

The ability to differentiate between repeated and novel events represents a fundamental property of the visual system. Neural responses are typically reduced upon stimulus repetition, a phenomenon called Repetition Suppression (RS). On the contrary, following a novel visual stimulus, the neural response is generally enhanced, a phenomenon referred to as Novelty Detection (ND). Here, we aimed to investigate the impact of early deafness on the oscillatory signatures of RS and ND brain responses. To this aim, electrophysiological data were acquired in early deaf and hearing control individuals during processing of repeated and novel visual events unattended by participants. By studying evoked and induced oscillatory brain activities, as well as inter-trial phase coherence, we linked response modulations to feedback and/or feedforward processes. Results revealed selective experience-dependent changes on both RS and ND mechanisms. Compared to hearing controls, early deaf individuals displayed: (i) greater attenuation of the response following stimulus repetition, selectively in the induced theta-band (4–7 Hz); (ii) reduced desynchronization following the onset of novel visual stimuli, in the induced alpha and beta bands (8–12 and 13–25 Hz); (iii) comparable modulation of evoked responses and inter-trial phase coherence. The selectivity of the effects in the induced responses parallels findings observed in the auditory cortex of deaf animal models following intracochlear electric stimulation. The present results support the idea that early deafness alters induced oscillatory activity and the functional tuning of basic visual processing.

The effect of electrode configuration and duration of deafness on threshold and selectivity of responses to intracochlear electrical stimulation.

This report examines the effects of intracochlear electrode configuration and mode of stimulation (bipolar or monopolar) on neural threshold and spatial selectivity in the inferior colliculus (IC) of the cat. Single and multiunit IC recordings were made in three groups of animals; acutely deafened adults (controls), neonatally deafened animals studied at 6 to 18 months of age and neonatally deafened cats studied at 2.5 to 6.5 years. Response thresholds were plotted versus IC depth to measure the spatial distribution of responses. The response selectivity for each stimulating configuration was defined as the width of the resulting spatial tuning curve (STC) measured at 6 dB above threshold. Spiral ganglion cell (SG) survival was examined histologically in all neonatally deafened animals and correlated with physiological results. Animals studied at less than 1.5 years had SG densities of 23.5%-64.4% of normal (mean=42.7%) while animals studied at greater than 2.5 years had densities of 5.1%-18.3% of normal (mean=9.9%). Electrophysiological results include the following. (1) Monopolar thresholds were 7-8 dB lower than bipolar thresholds in the same animals. (2) Varying the configuration of bipolar contacts (measured as radial, offset radial and longitudinal pairs) did not systematically affect IC threshold in either controls or short-term neonatally deafened animals. In contrast, the long-term neonatally deafened animals showed a difference in threshold with each configuration. (3) The spatial distributions (Q(6 dB)) of responses to bipolar stimulation were approximately 40% more restricted than those for monopolar stimulation. (4) The spatial selectivity of neonatally deafened animals studied at ages up to 1.5 years was equal to that of control animals with normal auditory experience. However, selectivity was degraded in the older animals. (5) Selectivity was decreased in some animals with the longitudinal bipolar configuration and multiple response peaks were seen in several cases using this stimulus configuration.

Modulation of P-CREB and expression of c-fos in cochlear nucleus and superior olive following electrical intracochlear stimulation.

Investigating activity-dependent plasticity in the auditory brain stem of the adult rat, we observed that electrical intracochlear stimulation led to a tonotopically localized modulation of the phosphorylation of the cAMP response element binding protein (CREB) and an equally localized expression of the immediate early gene product c-Fos in cochlear nucleus and superior olive. As P-CREB is thought to act as transcription factor on one promoter site of the c-fos gene, we compared immunolabeling for P-CREB and c-fos in adjacent brain sections. Following 2h sustained stimulation in previously deafened animals, labelling for P-CREB declined in regions where c-Fos labelling increased. This suggests that the level or state of P-CREB (e.g. whether it is phosphorylated or not) are affected by intracochlear stimulation in a process that appears to be linked to the stimulation-dependent expression of c-Fos in auditory brain stem nuclei.

Resolution of Single Deviant Intervals in Periodic Stimuli by Auditory Cortex Neurons: Comparison of Intracochlear Electric Pulse and Acoustic Click Stimulation

Responses of neurons in the primary auditory cortex were compared in gerbils receiving intracochlear electric or acoustic stimulation. Stimuli were trains of periodic electric pulses or of acoustic clicks. Interspersed between intervals of equal length were single intervals which were longer, by some Δt. The Δt and the repetition rate of these prolonged intervals were varied. The degree of synchronization of spikes to the regular occurrences of prolonged intervals was quantified. While thresholds for synchronized responses to Δt (at Δt repetition rates of 4–6 Hz) were about a hundredfold higher for electric (about 5–10 ms) than for acoustic stimulation (about 30 s), Δt repetition rate response functions were similar for both types of stimulation. The results suggest the feasibility of coding brief acoustic transients by prolonged intervals in electric pulse trains with high pulse repetition rates, which could be another useful strategy for cochlear implants.

Activity-Dependent Plasticity in the Adult Auditory Brainstem

Over the past few years we have studied the plasticity of the adult auditory brainstem in the rat following unilateral changes to the pattern of sensory activation, either by intracochlear electrical stimulation or by deafening. We discovered that modifications to afferent activity induced changes in the molecular composition and cellular morphology throughout the auditory brainstem, including its major centers: the cochlear nucleus complex, the superior olivary complex, and the inferior colliculus. The time window studied ranged from 2 h to over 1 year following induction of changes to afferent activity. The molecular markers employed include the NMDA receptor subunit type 1, the cAMP response element binding protein (CREB), the immediate early gene products c-Fos, c-Jun and Egr-1, the growth and plasticity-associated protein GAP-43 and its mRNA, the calcium binding protein calbindin, the cell adhesion molecule integrin-α₁, the microtubule-associated protein MAP-1b, and the neurofilament light chain (NF-L). As a consequence of the specific electrical stimulation of the auditory afferents or the loss of hearing, a cascade of events is triggered that apparently modifies the integrative action and computational abilities of the central auditory system. An attempt is made to relate the diverse phenomena observed to a common molecular signaling network that is suspected to bridge sensory experience to changes in the structure and function of the brain. Eventually, a thorough understanding of these events will be essential for the specific diagnosis of patients, optimal timing for implantation, and suitable parameters for running of a cochlear implant or an auditory brainstem implant in humans. In this report an overview of the results obtained in the past years in our lab is presented, flanked by an introduction into the history of plasticity research and a model proposed for intracellular signal cascades related to activity-dependent plasticity.

Expression of NMDA, AMPA and GABA A receptor subunit mRNAs in the rat auditory brainstem. II. Influence of intracochlear electrical stimulation

We investigated the effects of intracochlear electrical stimulation (ICES) on auditory pathways of neonatal rat deafened by daily amikacin injections. Expression of mRNAs encoding ionotropic glutamate receptor subunits such as α-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) and N-methyl- D-aspartate (NMDA), and γ-aminobutyric acid type A (GABA A) receptor subunits was assessed by in situ hybridization in the dorsal (DCN) and the ventral cochlear nucleus (VCN) and in the central nucleus of the inferior colliculus (CNIC). After 15 days of daily unilateral ICES, the expressions of NR1, NR2b and NR2c subunits of NMDA receptor, that of GluRA, B, C, D flop isoforms of AMPA receptor and that of some GABA A subunits (α1, β1, γ1, γ2) were increased bilaterally in the DCN, VCN and the CNIC. These changes last over a week after stimulation for only NR1 and NR2c. These modifications might be related to long lasting synaptic plasticity of brainstem auditory pathways. As far as analogy to deaf children can be made, early electrical stimulation might be of interest to maintain neuronal networks.

Reduction in excitability of the auditory nerve following electrical stimulation at high stimulus rates: V. Effects of electrode surface area

High rate intracochlear electrical stimulation at high intensities can induce significant reductions in the excitability of the auditory nerve as measured by a decrement in the amplitude of the electrically evoked auditory brainstem response (EABR). Such changes are primarily associated with stimulus induced neuronal activity, although direct current (DC) can also contribute. We examined the extent of stimulus induced change in auditory nerve excitability using large surface area platinum electrodes (‘high-Q’ electrodes). These electrodes have a surface area ∼70 times greater than standard Pt electrodes of the same geometric area, resulting in lower DC and charge density (charge/electrode surface area) for a common stimulus. Guinea pigs were bilaterally implanted with either high-Q or standard Pt electrodes, and unilaterally stimulated for 2 h using stimulus intensities of 12 dB or 20–30 dB above EABR threshold (0.34 μC/phase) at stimulus rates of 200, 400, or 1000 pulses per second (pps). EABRs were recorded before and following the acute stimulation. While there were significant reductions in EABR amplitudes and elevated EABR thresholds following stimulation at 12 dB above threshold using 400 and 1000 pps delivered to standard Pt electrodes, there were fewer or no significant changes in the post-stimulus EABR amplitude and threshold using high-Q electrodes under equivalent stimulus conditions. At a higher stimulus intensity (20–30 dB above EABR threshold), no reduction in EABR amplitude was observed at 200 pps for both stimulating electrodes. However, EABRs were reduced significantly at 400 and 1000 pps. There was significantly greater EABR recovery following stimulation using high-Q electrodes compared with standard Pt electrodes at 400 ( P<0.05) and 1000 pps ( P<0.05). These data indicate that large surface area electrodes can significantly reduce stimulus induced changes in auditory nerve excitability, and may therefore have important clinical application.

Cochleotopic fos immunoreactivity in cochlea and cochlear nuclei evoked by bipolar cochlear electrical stimulation

Fos-like immunoreactivity evoked by basal, second or apical turn bipolar intracochlear electrical stimulation was evaluated in the spiral ganglion and cochlear nuclei. At stimulation levels of six times the electrically evoked auditory brain stem response thresholds, immunoreactive neurons were observed at appropriate discrete cochleotopic regions relative to stimulation site. The number of neurons increased with stimulus level and closely correlated to wave I amplitude. At 10 times thresholds, some spread in fos-like immunoreactivity to adjacent cochlear turns was found. However, fos-like immunoreactivity at this high level of stimulation still clearly showed a differential distribution in density of expression. These results indicated that the restricted topographic distribution of activity evoked by high levels of electrical stimulation is initiated at first order primary neurons of the system. For the profoundly deaf with cochlear implants, this indicates that place (channel) information can be maintained in the spiral ganglion and central nervous system even at very high levels of electrical stimulation. Together with our previous studies, these results indicate that fos provides a marker which can be used for evaluation of extent and pattern of cellular activation throughout the central auditory pathways, including activation of auditory nerve cells.

Chronic electrical stimulation by a cochlear implant promotes survival of spiral ganglion neurons after neonatal deafness

This investigation examined the consequences of neonatal deafness and chronic intracochlear electrical stimulation delivered by a cochlear implant during maturation. Kittens were bilaterally deafened by an ototoxic drug administered daily for 2 weeks immediately after birth. Unilateral electrical stimulation was initiated at 7-10 weeks of age and continued over periods of 22-47 weeks (4 hours/day; 5 days/week). Bipolar intracochlear electrodes delivered one of several different electrical signals designed to be temporally challenging to the central auditory system. Morphometric evaluation of spiral ganglion (SG) cell somata within Rosenthal's canal demonstrated a mean of approximately 50% of normal cell density maintained in the chronically stimulated ears, compared with approximately 30% on the control deafened side. This 20% difference in density was highly significant and was greater than differences reported in earlier studies using 30 pps stimulation delivered by either intracochlear bipolar or round window monopolar electrodes. However, the duration of stimulation was also longer in the present study, so it is unclear to what extent the nature of the temporally challenging stimulation vs. its duration contributed to the marked increase in survival. Measurements of the SG cell somata revealed a pronounced decrease in cell diameter in neonatally deafened cats studied about 1 year after deafening, and an additional decrease after long-term deafness (2.5-6.5 years). Furthermore, in the cochlear regions with the greatest stimulation-induced differences in SG cell density, direct measurements of cross-sectional soma area of the largest cells revealed that cells were significantly larger in the stimulated ears. Thus, in addition to the marked increase in the number of surviving SG cells, larger soma area contributed modestly to the pronounced increase in neural density following chronic electrical stimulation.

Reduction in excitability of the auditory nerve following electrical stimulation at high stimulus rates. IV. Effects of stimulus intensity

High rate intracochlear electrical stimulation using stimulus intensities well above clinical limits can induce a significant reduction in the excitability of the auditory nerve as measured by a reduction in the amplitude of the electrically evoked auditory brainstem response (EABR). The purpose of the present study was to assess the effect of stimulus intensity on these stimulus induced changes by comparing the effects of acute stimulation using stimulus intensities within normal clinical levels (6 dB and 12 dB above EABR threshold) and significantly above normal clinical levels (>20 dB above EABR threshold; 0.34 μC/phase). Stimulus rates of 200, 400, or 1000 pulses/s (pps) were delivered to bipolar scala tympani electrodes. EABRs were recorded before and periodically following 2 h of continuous stimulation. No reduction in EABR amplitude was observed following stimulation at 6 dB above EABR threshold for the three stimulus rates examined. However, EABRs were reduced when stimulated at 12 dB above EABR threshold at 400 pps, and significantly reduced when stimulated at a rate of 1000 pps. Immediate post-stimulus response amplitudes of wave III were 63% and 35% of the pre-stimulus amplitude at 400 and 1000 pps respectively. More significant reductions in EABR amplitude were observed following stimulation at levels more than 20 dB above EABR threshold for both 400 and 1000 pps stimuli. Our findings indicate that stimulus induced changes in EABR amplitude are related to both stimulus rate and stimulus intensity. Moreover, stimulation using intensities within the normal clinical range show little evidence of prolonged reductions in auditory nerve excitability at stimulus rates of up to 1000 pps.

Fos-like immunoreactivity in the auditory brain stem evoked by bipolar intracochlear electrical stimulation: effects of current level and pulse duration

Fos-like immunoreactivity was used to compare the auditory brain stem excitation elicited by bipolar electrical stimulation of the cochlea at various current levels relative to the electrically evoked auditory brain stem response threshold for a 50-μs/phase monophasic pulse. Fos-like immunoreactive cells were labeled in primary auditory brain stem regions. The distribution of labeled cells was restricted to regions known to be cochleotopically related to the stimulated region of the scala tympani. Some labeled cells were observed at 2× electrically evoked auditory brain stem response threshold. The number, density and spatial distribution of labeled cells were quantified in the dorsal cochlear nucleus and inferior colliculus, and found to increase with increasing level of stimulation. For 50-μs pulses, the location of labeled neurons remained reasonably restricted to narrow bands within each region until the 10× level of stimulation (20 dB above electrically evoked auditory brain stem response threshold) was reached. While a monotonic increase in Fos-like immunoreactivity with increasing stimulus level was observed in most nuclei, for cells of the superficial layer of the dorsal cochlear nucleus, a non-monotonic change with increasing stimulus level was seen. This dorsal cochlear nucleus non-monotonicity may indicate that, at higher levels of stimulation, a secondary indirect inhibitory input, probably associated with activation of deep layer dorsal cochlear nucleus cells, reduces excitatory responses at the superficial layer of the dorsal cochlear nucleus. Electrically evoked auditory brain stem response and Fos expression showed parallel changes as a function of stimulus level and pulse duration. The data indicate that discrete activation of cell populations within the central auditory pathways can occur with bipolar electrical stimulation to the highest levels of stimulation typically useful in humans. The data also indicate a close, but not identical, quantitative relationship between Fos-like immunoreactivity and electrophysiological response amplitude. These findings support the view that a study of Fos-like immunoreactivity can provide a powerful and quantitative tool for study of the dynamic response characteristics of cells of the central auditory system to electrical stimulation at suprathreshold levels. The data suggest that there is a monotonic increase in the number of neurons responsive to intracochlear electrical stimulation as a function of stimulus level, at least through the upper half of the dynamic range, but that this increase does not result in a complete loss of spatial selectivity. Coupled with previous psychophysical studies, these results suggest that the increase in the number of activated neurons is functionally beneficial, resulting in improved discrimination of changes in the electrical signals.

Chronic Electrical Stimulation of the Auditory Nerve using Non-charge-balanced Stimuli

This study was designed to evaluate the pathophysiological response of the cochlea following long-term intracochlear electrical stimulation using a poorly charge-balanced stimulus regime, leading to direct current (DC) levels >0.1

Intracellular responses of the rat anteroventral cochlear nucleus to intracochlear electrical stimulation

The anteroventral cochlear nucleus (AVCN) is the first central processing site for acoustic information. The influence and extent of convergent auditory nerve input to AVCN neurons was investigated using brief (<0.2 ms) intracochlear electrical activation of spiral ganglion cells. In 40 neurons recorded in vivo , the major intracellular response to stimulation was an excitatory postsynaptic potential (EPSP) with short latency (∼1 ms) and fast rise time (<1 ms). Graduated EPSP amplitude increases were also seen with increasing stimulation strength resulting in spike generation. Hyperpolarization followed excitation in most neurons, its extent distinguished three response types: Type I showed no hyperpolarization; Type II and Type III displayed short (<10 ms) and long (>19 ms) duration hyperpolarization, respectively. Hyperpolarization was attributed to an inhibitory postsynaptic potential (IPSP) in addition to spike after hyperpolarization. Neurobiotin filling identified Type I and II neurons as stellate and Type III as bushy cells. These results suggests that AVCN neurons receive direct, possibly convergent, excitatory input from auditory nerves emanating from spiral ganglion cells with hyperpolarization resulting from polysynaptic inhibitory input.

Spatial resolution of cochlear implants: the electrical field and excitation of auditory afferents

This paper investigates the spatial resolution of electrical intracochlear stimulation in order to enable further refinement of cochlear implants. For this purpose electrical potential distributions around a conventional human intracochlear electrode (NUCLEUS-22) were measured in a tank, in cat cadaver cochleae and in living cat cochleae. Potential gradients were calculated where of importance. The values were compared to spatial tuning curves from cat primary auditory afferents in electrical mono-, bi-, and various tripolar stimulation modes. Finally, a lumped element model was developed to elucidate the single fiber data. Tank potential measurements show the principal features of the different stimulation modes but are not sufficient to explain all the features of experimental data from single fibers. Intracochlear potential measurements indicate an increase in spatial resolution in an apical direction. The single fiber data also confirm that a tripolar stimulus configuration provides significantly better spatial resolution than any other stimulation mode presently in use.

Effects of chronic electrical stimulation on spiral ganglion neuron survival and size in deafened kittens.

We have studied spiral ganglion cell (SGC) survival and soma size in neonatally pharmacologically deafened kittens. They were implanted with a four-electrode array in the left cochlea at 100 to 180 or more days of age. Eight animals were chronically stimulated approximately 1000 hours over approximately 60 days with charge-balanced, biphasic current pulses; three were unstimulated controls. Using three-dimensional computer-aided reconstruction of the cochlea, the SGC position and cross-sectional area were stored. SGC position was mapped to the organ of Corti by perpendicular projections, starting from the basal end. The basal region of the cochlea was divided into three 4-mm segments. SGC survival (number per 0.1 mm of the length of the organ of Corti) and soma size for stimulated cochleae were compared statistically with implanted but unstimulated cochleae. There was no evidence of an effect of electrical stimulation on SGC survival under this protocol and with this duration. On the other hand, the cell size on the stimulated side was significantly larger than the control side in the middle segment (4 to 8 mm from the basal end). SGCs undergo a reduction in size after prolonged auditory deprivation; however, these changes may be partially moderated after chronic intracochlear electrical stimulation.

Chronic electrical stimulation of the auditory nerve at high stimulus rates: a physiological and histopathological study

A major factor associated with recent improvements in the clinical performance of cochlear implant patients has been the development of speech-processing strategies based on high stimulation rates. While these processing strategies show clear clinical advantage, we know little of their long-term safety implications. The present study was designed to evaluate the physiological and histopathological effects of long-term intracochlear electrical stimulation using these high rates. Thirteen normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods of up to 2100 h using either two pairs of bipolar or three monopolar stimulating electrodes. Stimuli consisted of short duration (25–50 μs/phase) charge-balanced biphasic current pulses presented at 1000 pulses per second (pps) per channel for monopolar stimulation, and 2000 pps/channel for bipolar stimulation. The electrodes were shorted between current pulses to minimize any residual direct current, and the pulse trains were presented using a 50% duty cycle (500 ms on; 500 ms off) in order to simulate speech. Both acoustic (ABR) and electrical (EABR) auditory brainstem responses were recorded periodically during the chronic stimulation program. All cochleas showed an increase in the click-evoked ABR threshold following implant surgery; however, recovery to near-normal levels occurred in approximately half of the stimulated cochleas 1 month post-operatively. The use of frequency-specific stimuli indicated that the most extensive hearing loss generally occurred in the high-frequency basal region of the cochlea (12 and 24 kHz) adjacent to the stimulating electrode. However, thresholds at lower frequencies (2, 4 and 8 kHz), appeared at near-normal levels despite long-term electrode implantation and electrical stimulation. Our longitudinal EABR results showed a statistically significant increase in threshold in nearly 40% of the chronically stimulated electrodes evaluated; however, the gradient of the EABR input/output (I/O) function (evoked potential response amplitude versus stimulus current) generally remained quite stable throughout the chronic stimulation period. Histopathological examination of the cochleas showed no statistically significant difference in ganglion cell densities between cochleas using monopolar and bipolar electrode configurations (P = 0.67), and no evidence of cochlear damage caused by high-rate electrical stimulation when compared with control cochleas. Indeed, there was no statistically significant relationship between spiral ganglion cell density and electrical stimulation (P = 0.459), or between the extent of loss of inner (IHC, P = 0.86) or outer (OHC, P = 0.30) hair cells and electrical stimulation. Spiral ganglion cell loss was, however, influenced by the degree of inflammation (P = 0.016) and electrode insertion trauma. These histopathological findings were consistent with the physiological data. Finally, electrode impedance, measured at completion of the chronic stimulation program, showed close correlation with the degree of tissue response adjacent to the electrode array. These results indicated that chronic intracochlear electrical stimulation, using carefully controlled charge-balanced biphasic current pulses at stimulus rates of up to 2000 pps/channel, does not appear to adversely affect residual auditory nerve elements or the cochlea in general. This study provides an important basis for the safe application of improved speech-processing strategies based on high-rate electrical stimulation.

Optical Imaging of Neural Activity in Auditory Cortex Induced by Intracochlear Electrical Stimulation

Little is known about the representation of electrically evoked activity in the auditory cortex. We observed evoked activity in guinea pig auditory cortex evoked by acoustical and electrical stimulation to the cochlea by optical imaging with the aid of a voltage-sensitive dye. Light signals from the cortex were recorded with a 12 ° 12 array of photodiodes, and transferred to the spatio-temporal images by every 0.57 ms. The activity by pure tones was shown spatio-temporally through tonotopical organization in the cortex according to the sound frequencies. The tonotopic responses were dynamically changed. When the cochlea was stimulated with single electrical pulses, focal activities were observed in the cortex as spatio-temporal patterns. Activated cortical regions were not sharply localized, but varied with stimulating positions of the cochlea. The curves of response magnitude versus stimulus intensity showed the narrow dynamic range, and that of latency was almost constant. These results were significantly different from those for normal sound stimulation.