Characterization of depolarization-evoked ERG K currents in interstitial cells of Cajal.

Interstitial cells of Cajal (ICC) harbour the ether-a-go-go related gene (ERG) channel as shown by its characteristic rapidly deactivating current upon hyperpolarization. This property, however, does not explain the marked increase in cell excitability by ERG channel blockers, namely an increase in slow wave plateau duration and action potential generation. The objective of the present study was to characterize the depolarization-activated, E4031-sensitive ERG currents in murine ICC within a range of physiologically relevant membrane potentials. Whole cell currents were recorded from ICC isolated from murine neonatal jejunum, superfused with a physiological salt solution and with high intracellular Cs(+) to block most other K(+) currents. Upon depolarizing the cell from the resting membrane potential (approximately -60 mV) towards the region of the slow wave plateau (approximately -30 mV), significant sustained (window) current was generated between the potentials of -40 to 0 mV (maximal at -30 mV) and inhibited by the ERG specific blocker E4031. Channel activation followed by rapid inactivation produced a steady state conductance at -30 mV which was 51.6 +/- 11% of the hyperpolarization-evoked peak conductance value at -100 mV. When the cell repolarized from -30 mV, again, significant currents were generated, indicating recovery from inactivation, a typical characteristic of ERG channels. These data provide evidence that the ERG channel is of significance in the regulation of ICC excitability and provide the mechanism by which ERG channel blockade increases the slow wave duration.

Short-term auditory memory in children using cochlear implants and its relevance to receptive language.

The aim of this study was to assess auditory sequential, short-term-memory (SSTM) performance in young children using cochlear implants (CI group) and to examine the relationship of this performance to receptive language performance. Twenty-four children, 5 to 11 years old, using the Nucleus 22-electrode cochlear implant, were tested on a number of auditory and visual tasks of SSTM. The auditory memory tasks were designed to minimize the effect of auditory discrimination ability. Stimuli were chosen that children with cochlear implants could accurately identify with a reaction time similar to that of a control group of children with normal hearing (NH group). All children were also assessed on a receptive language test and on a nonverbal intelligence scale. As expected, children using cochlear implants demonstrated poorer auditory and visual SSTM skills than their hearing peers when the stimuli were verbal or were pictures that could be readily labeled. They did not differ from their peers with normal hearing on tasks where the stimuli were less likely to be verbally encoded. An important finding was that the CI group did not appear to have a sequential memory deficit specific to the auditory modality. The difference scores (auditory minus visual memory performance) for the CI group were not significantly different from those for the NH group. SSTM performance accounted for significant variance in the receptive language performance of the CI group. However, a forward stepwise regression analysis revealed that visual spatial memory (one of the subtests of the nonverbal IQ test) was the main predictor of variance in the language scores of the children using cochlear implants.

Rate-of-processing ability in children using cochlear implants and its relevance to speech perception.

The aim was to assess the ability of young children using cochlear implants to process a change in place of stimulation under conditions of shortened stimulus duration and shortened interstimulus interval. The study investigated whether or not this ability accounted for a significant amount of the variance in the speech performance of the children additional to the variance accounted for by electrode discrimination ability (measured in a previous study). An adaptation of the play audiometry procedure was used to assess 'rate-of-processing' ability in 17 children aged between 4 and 10 years. Initially the child was required to respond with a game-like motor response when a repeating stimulation on a reference electrode 'changed' to a different electrode in relatively 'slow' conditions. The child was then required to respond to the 'change', when the duration of the stimuli and the time interval between the stimuli were decreased. All but one of the children using cochlear implants scored significantly above chance for all conditions of stimulus duration and interstimulus interval assessed. That is, they were able to discriminate place pitch changes when these changes occurred more rapidly in time. A stepwise regression was computed to determine the relative contributions of a number of variables, including rate-of-processing ability, in accounting for variance in the children's speech perception performance (measured in a previous study). Rate-of-processing ability did not account for any variance additional to that accounted for by electrode discrimination ability, which was found to be the most significant predictor of speech perception performance for this group of children in the previous study.

Optimizing electrode and filter selection in cochlear implant speech processor maps.

This study examined two hypotheses: that speech understanding of cochlear implantees could be improved by removing electrodes that exhibit nontonotopic percepts from the speech processor map and that speech understanding could be improved by extending the range of high frequencies that are mapped to the electrodes. Electrodes producing nontonotopic percepts were identified using a multidimensional scaling procedure with seven users of the Nucleus CI22 implant and Spectra processor. Two experimental maps were created with those electrodes removed: the first using the same set of filters as their clinical map and the second using the complete set of filters available. After periods of take-home experience, speech perception was tested and compared for the two experimental maps and their own clinical map. It was found that removing nontonotopic electrodes did not improve speech perception, possibly due to the deleterious side effect of shifting the frequency-to-electrode allocation. Also, extending the high-frequency range of the map did not improve speech perception, possibly due to the poor sensitivity of this processor to high-frequency sounds.

Loudness summation for pulsatile electrical stimulation of the cochlea: effects of rate, electrode separation, level, and mode of stimulation.

The aim of these two experiments was to gain systematic data on the amount of loudness summation measured for dual-electrode stimuli with varying temporal and spatial separation of current pulses. Loudness summation is important in the implementation of speech processing strategies for implantees. However, the loudness mapping functions used in current speech processors utilize psychophysical data (thresholds and comfortable loudness levels) derived using single-electrode stimuli, and do not take into account the temporal and spatial patterns of the speech processor output. In the first experiment, the current reduction required to equalize the loudness of a dual-electrode stimulus to that of its component (and equally loud) single-electrode stimuli was measured for three electrode separations (0.75, 2.25, and 7.5 mm), three repetition rates (250, 500, and 1000 Hz), and two loudness levels (comfortably loud, and mid-dynamic range). It was found that electrode separation had little effect on loudness summation, except for interactions with level and rate effects at the smallest separation. More current adjustment (in dB) was required for higher rates and lower levels of stimulation. The second experiment investigated the effects of mode (monopolar versus bipolar) and pulse duration on loudness summation. More current adjustment was required in bipolar mode than in monopolar mode at the lower level only. The main effects in both experiments, and their interactions, are consistent with a loudness model in which the neural excitation density is first obtained by temporal integration of excitation at each cochlear place, then converted to specific loudness via a nonlinear relationship, and finally integrated over cochlear place to obtain the loudness. The two important features which affect the loudness relationships in dual-electrode stimulation in this model are the shape of the excitation density function and the amount by which the neural spike probability per pulse is reduced in areas of overlapping excitation due to refractory effects.

The relationship between speech perception and electrode discrimination in cochlear implantees.

Speech Intelligibility Index (SII) procedures were used to measure the amount of speech information perceived in five frequency bands (170-570, 570-1170, 1170-1768, 1768-2680, and 2680-5744 Hz) by 15 users of the Cochlear Ltd. CI-22M implant and Spectra-22/SPEAK processor. The speech information perceived was compared to that perceived by normal-hearing listeners. The ability of these subjects to discriminate between stimulation on adjacent electrodes corresponding to each frequency band was also investigated, using a 4IFC procedure with random current level variations of between 0% and 60% of the dynamic range. Relative to normal-hearing listeners, speech information was, on average, significantly more reduced in the four frequency regions between 170 and 2680 Hz than in the region 2680-5744 Hz. There was a significant correlation between electrode discrimination ability (when the random level variation encompassed 20% or more of the dynamic range) and the amount of speech information perceived in the four frequency regions between 170 and 2680 Hz. There was no such correlation in the region 2680-5744 Hz, regardless of the extent of random level variation. These results indicate that speech information in the low to medium frequencies is more difficult for implantees to perceive, that this difficulty is correlated with the difficulty in discriminating electrode place in the presence of random loudness variations, and that fine spectral discrimination may be relatively more important in the vowel-formant regions than in higher frequency regions.

Central auditory processing in patients with auditory hallucinations.

OBJECTIVE: Data from a full assessment of auditory perception in patients with schizophrenia were used to investigate whether auditory hallucinations are associated with abnormality of central auditory processing. METHOD: Three groups of subjects participated in auditory assessments: 22 patients with psychosis and a recent history of auditory hallucinations, 16 patients with psychosis but no history of auditory hallucinations, and 22 normal subjects. Nine auditory assessments, including auditory brainstem response, monotic and dichotic speech perception tests, and nonspeech perceptual tests, were performed. Statistical analyses for group differences were performed using analysis of variance and Kruskal-Wallis tests. The results of individual patients with test scores in the severely abnormal range (more than three standard deviations from the mean for the normal subjects) were examined for patterns that suggested sites of dysfunction in the central auditory system. RESULTS: The results showed significant individual variability among the subjects in both patient groups. There were no group differences on tests that are sensitive to low brainstem function. Both patient groups performed poorly in tests that are sensitive to cortical or high brainstem function, and hallucinating patients differed from nonhallucinating patients in scores on tests of filtered speech perception and response bias patterns on dichotic speech tests. Six patients in the hallucinating group had scores in the severely abnormal range on more than one test. CONCLUSIONS: Hallucinations may be associated with auditory dysfunction in the right hemisphere or in the interhemispheric pathways. However, comparison of results for the patient groups suggests that the deficits seen in hallucinating patients may represent a greater degree of the same types of deficits seen in nonhallucinating patients.

Electrode discrimination and speech perception in young children using cochlear implants.

OBJECTIVE: The aim was to determine the efficacy of a child-appropriate procedure to assess electrode discrimination ability in young children using cochlear implants and to investigate the relationship of electrode discrimination ability and speech perception performance in children implanted at a young age. DESIGN: An adaptation of the play audiometry procedure was used to assess electrode discrimination in seventeen 4- to 10-yr-old children. The children were required to respond with a game-like motor response when a repeating stimulation on a reference electrode "changed" to a different electrode. They were also assessed on a speech feature discrimination test, a closed-set word recognition test and a nonverbal intelligence task. RESULTS: Sixty-five percent of subjects demonstrated ability to discriminate adjacent electrodes in mid and apical regions of the cochlea, whilst the remaining subjects needed electrode separations of between two and nine electrodes for successful discrimination. In a forward stepwise regression analysis electrode discrimination ability was found to be the strongest factor in accounting for variance in the speech perception scores. Subject variables such as duration of deafness, nonverbal intelligence and implant experience did not significantly account for further variance in the speech perception scores for this group of children. CONCLUSIONS: Electrode discrimination ability was the strongest factor in predicting performance on speech perception measures in a group of children using cochlear implants.

Effect of current level on electrode discrimination in electrical stimulation.

The effect of the stimulation intensity (current amplitude) on the ability to discriminate electrodes was tested in an experiment with four adult users of the Nucleus-22 cochlear implant. A total of 12 adjacent pairs of electrodes were used in the four-interval forced-choice discrimination task with random current variation. Tests were carried out at three average stimulation levels: 40 and 70% of the dynamic range and close to maximum comfortable loudness. Analysis of variance revealed a significant (P<0.0001) deterioration in electrode discrimination with a decreasing level. However, the overall effect was very small, representing a deterioration in the discrimination score of only 18% correct from the highest to lowest levels tested. The reason for the small deterioration in discriminability with a decreasing level is difficult to determine from this experiment, however, the results are consistent with the hypothesis that changes in the 'peak' or 'edge' of the excitation pattern are more important for discrimination tasks than the relative amount of non-overlap of the excitation areas from the two electrodes.

The perceptual effects of current pulse duration in electrical stimulation of the auditory nerve.

In cochlear implants employing pulsatile stimulation, loudness is controlled by current amplitude and/or pulse duration. Five experiments were conducted with cochlear implantees to investigate the hypothesis that perceptual effects other than loudness result from changes in pulse duration for durations from 50 to 266 microseconds. In experiment 1, five subjects' ability to discriminate equally loud pulse trains employing differing pulse durations was measured at four electrode positions. In 11 of the 20 cases, subjects could significantly discriminate these stimuli. In experiments 2 and 3, discrimination was measured of dual-electrode stimuli which differed in overall temporal pattern but had an equal temporal pattern on each of the individual electrodes (separated by 0 to 9 mm). Discrimination was compared for stimuli employing short or long pulse durations and, in experiment 3, employing different pulse durations on each electrode. When the pulse duration was longer, six out of seven subjects could either combine temporal information across electrode positions at wider electrode separations (experiment 2) or had better discrimination at the same electrode separation (experiment 3). This result was consistent with the hypothesis that longer pulse durations result in a greater spread of excitation than equally loud stimuli using shorter pulse durations. In experiment 4, pulse rate discrimination was compared for stimuli with differing pulse durations, and in four out of five subjects, there was no effect of pulse duration. Finally, the dB change in current per doubling of pulse duration for threshold and equally loud stimuli was calculated for nine subjects (52 electrodes). Values ranged from -5.9 to -2.0 dB/doubling, and were significantly correlated with the absolute intensity of the stimulus. This result was hypothesized to be due to a relationship between the neural charging characteristics and the distance of the excited neural elements from the electrode.

Dual temporal pitch percepts from acoustic and electric amplitude-modulated pulse trains.

Two experiments examined the perception of unmodulated and amplitude-modulated pulse trains by normally hearing listeners and cochlear implantees. Four normally hearing subjects listened to acoustic pulse trains, which were band-pass filtered between 3.9 and 5.3 kHz. Four cochlear implantees, all postlinguistically deaf users of the Mini System 22 implant, listened to current pulse trains produced at a single electrode position. In the first experiment, a set of nine loudness-balanced unmodulated stimuli with rates between 60 and 300 Hz were presented in a multidimensional scaling task. The resultant stimulus spaces for both subject groups showed a single dimension associated with the rate of the stimuli. In the second experiment, a set of ten loudness-balanced modulated stimuli was constructed, with carrier rates between 140 and 300 Hz, and modulation rates between 60 and 150 Hz. The modulation rates were integer submultiples of the carrier rates, and each modulation period consisted of one higher-intensity pulse and one or more identical lower-intensity pulses. The modulation depth of each stimulus was adjusted so that its pitch was judged to be higher or lower 50% of the time than that of an unmodulated pulse train having a rate equal to the geometric mean of the carrier and modulation rates. A multidimensional scaling task with these ten stimuli resulted in two-dimensional stimulus spaces, with dimensions corresponding to carrier and modulation rates. A further investigation with one normally hearing subject showed that the perceptual weighting of the two dimensions varied systematically with modulation depth. It was concluded that, when filtered appropriately, acoustic pulse trains can be used to produce percepts in normal listeners that share common features with those experienced by subjects listening through one channel of a cochlear implant, and that the central auditory system can extract two temporal patterns arising from the same cochlear location.

Loudness perception with pulsatile electrical stimulation: the effect of interpulse intervals.

The effect of interpulse intervals on the perception of loudness of biphasic current pulse trains was investigated in eight adult cochlear implantees at three different stimulus levels encompassing the psychophysical dynamic range. Equal-loudness contours and thresholds were obtained for stimuli in which two biphasic pulses were presented in a fixed repetition period (4 and 20 ms), and also for single-pulse/period stimuli with rates varying between 20 and 750 Hz. All stimuli were of 500-ms duration, and the phase durations of each pulse were 100 microseconds or less. The results of these experiments were consistent with predictions of a three-stage model of loudness perception, consisting of a peripheral refractory effect function, a sliding central integration time window, and a central equal-loudness decision device. Application of the model to the data allowed the estimation of neural refractory characteristics of the subjects' remaining peripheral neural population. The average neural spike probability for a 50-Hz stimulus was predicted to be about 0.77, with an associated neural refractory time of 7.3 ms. These predictions did not vary systematically with level, implying that the effect of increasing current level on loudness results more from recruitment of neurons than from any increase in average spike probability.

Musical pitch perception with electrical stimulation of the cochlea.

Studies were undertaken to investigate the ability of a user of the Nucleus multi-electrode cochlear implant to judge pitch in the context of musical intervals. The subject had qualified as a musical instrument tuner before he received his implant, and was able to judge the intervals between electrical sensations with neither training nor the guidance of familiar melodies. The procedures used were interval estimation, and interval production by the method of adjustment. The pitch of the electrical stimulation was controlled by varying the pulse repetition rate, the active electrode position, or two combinations of these parameters. Further studies employed sinusoidally amplitude modulated pulse trains with varying modulation frequency. The results showed that rate or modulation frequency could convey musical pitch information over a limited range (approximately two octaves). The data were directly comparable with the relationship between musical intervals and frequency for normal hearing. The pitch related to electrode place varied in accordance with the tonotopic organization of the cochlea, and also appeared to be able to support musical intervals. When both place and rate varied together, the place-related pitch was generally dominant. In all cases, the judgement of intervals tended to diverge from their acoustic counterparts as the intervals became larger.

The perception of temporal patterns for electrical stimulation presented at one or two intracochlear sites.

The question of how well the temporal structure in pulsatile electrical stimulation is perceived, and the nature of the information that may be conveyed by this temporal structure, is of importance to the further development of speech processing strategies for cochlear implants. The two experiments described here investigated the perception of temporal fine structure in amplitude modulated 1-kHz pulse trains, both when a single electrode position was used, and when the pulses alternated between two electrode positions. Five subjects with the Mini System 22 implant took part in these experiments. The amplitude modulations were constructed so that all dual-electrode stimuli had the same temporal pattern on each individual electrode but differed in the aggregate temporal pattern A hypothesis was investigated that subjects perceive the aggregate temporal pattern rather than the pattern at each individual electrode place, only when the electrodes are less than a critical distance apart. The first of these two experiments used a four-interval forced-choice task to measure the ability of subjects to detect changes in the aggregate temporal pattern. At electrode distances greater than 3 to 4 mm, subjects could no longer perceive the aggregate pattern, confirming the hypothesis. The second experiment used a single-interval pitch estimation task to test the hypothesis that the perceptual differences in temporal patterns measured in the previous experiment were classified similarly to rate pitch differences by the subjects. The results confirmed this hypothesis, and showed that the pitch of the modulated stimuli could be predicted by the expected inter-pulse intervals in the excited neural population.

The perceptual dimensions of single-electrode and nonsimultaneous dual-electrode stimuli in cochlear implantees.

The perceptual dimensions evoked by dual-electrode stimulation were investigated in four cochlear implantees. The dual-electrode stimulation consisted of biphasic current pulse trains, such that two intracochlear electrodes each received one pulse in a 250-Hz cycle. The experiments tested the hypothesis that perceptual qualities would be altered when there was an increased likelihood of interactions occurring between the two electrode places. The parameters of the stimulation which were manipulated to test this hypothesis were the time delay between the pulses on the two electrodes (2 ms and a value between 0.62 and 0.92 ms), the distance between the component electrode rings of each bipolar pair (3.75 mm and either 2.25 or 1.5 mm), and the distance between the two bipolar pairs in the dual-electrode stimuli (from 0.75 to 12.0 mm). Five set of 15 loudness balanced stimuli were created, each set having different stimulation parameters. These stimuli consisted of five single-electrode stimuli (a 250-Hz pulse train on each of five electrodes) and the ten dual-electrode stimuli formed by the combinations of those five electrodes. Two perceptual dissimilarity matrices were obtained for each subject and each set, and were analyzed using repeated nonmetric multidimensional scaling techniques. The resultant "stimulus spaces" were then examined to see how many perceptual dimensions the stimuli were best described by, and to what perceptual or stimulus qualities the dimensions might correspond. The results showed that the percept evoked by dual-electrode stimulation contained two main dimensions. Increasing the width of the current path to create substantially overlapping stimulation areas, or altering the temporal delay between the two electrodes, had very little effect on this percept. The position of the stimuli in the two-dimensional space was related to the distances of the two component electrodes along the electrode array. These results are relevant to speech processing strategies and electrode design for cochlear implants, as they imply that the creation of discrete, nonoverlapping areas of stimulation may not cause the percepts to be more distinct, and therefore may not necessarily lead to better speech perception.

Loudness ratio production by cochlear implantees using the spectral maxima sound processor.

The loudness growth characteristics of five users of the Mini System 22 implant and the Spectral Maxima Sound Processor were measured and compared with those of five normally hearing subjects. The main objective was to evaluate the suitability of the function employed in the sound processor that converts acoustic input levels of electrical stimulation. The method of loudness ratio production was used. The average result of the normally hearing subjects for halving and doubling loudness was 10.8 dB. The results of three of the implantees were comparable with those of the normally hearing subjects (average 8.83 dB), while those of the remaining subjects were quantitatively and qualitatively different. Investigation showed that altering the amplitude conversion function in the sound processor would not make the results of these two implantees more like those of the other subjects. However, it is possible that their responses were affected by the limited input dynamic range of the sound processor.

Loudness summation for two channels of stimulation in cochlear implants: effects of spatial and temporal separation.

An experiment with four implantees with the Mini System 22 device was undertaken to measure the loudness summation across two channels of stimulation, with stimuli in which the current pulses were delivered alternately to each channel. The effects of varying spatial separation, temporal separation, and extent of stimulation were investigated. It was found that the absolute amount of summation varied among subjects, and was in general independent of electrode separation, except for a reduction at zero separation. Widening of the spatial extent of the stimulation did not have a consistent effect. There was a reduction in summation for all subjects at zero electrode separation when the time between the two pulses was increased from less than 1 millisecond to 2 milliseconds. In conclusion, loudness summation did not appear to be highly dependent on parameters that affect the spatial current spread in the cochlea. Further study of the effect of temporal parameters on loudness may help to quantify interaction between stimulation channels.

Pitch matching of amplitude-modulated current pulse trains by cochlear implantees: the effect of modulation depth.

An experiment was conducted with four cochlear implantees, which investigated the pitch evoked by amplitude-modulating current pulse trains delivered to a single cochlear location. These stimuli produce a pitch percept which may be similar to that of acoustic stimuli such as modulated noise for modulation frequencies in the range 80-300 Hz, approximately. The experiments investigated the effect of modulation depth on the way pitch was matched to that of unmodulated pulse trains. The method of constant stimuli was used, in which the variable parameter was the rate of the unmodulated stimulus. The modulated stimuli comprised pulses having one of two possible current values, with the higher value occurring once in every modulation period. The results showed that the matched rate fell exponentially from a value close to the carrier rate towards a value equal to the modulation frequency as the modulation depth increased. The results were compared to the predictions of a simple model in which the matched rate corresponded to a weighted average of carrier and modulation frequencies, with the weightings proportional to the number of neurons firing at each of these frequencies. The results agreed with the predictions of the model reasonably well, except in cases where the carrier rate was 700 Hz or higher, and for one subject at the highest intensity level.

Pitch percepts associated with amplitude-modulated current pulse trains in cochlear implantees.

The percepts elicited by electrical stimulation of auditory neurons by trains of amplitude-modulated current pulses were studied in a group of six cochlear implant users. Modulation frequencies of 100, 150, and 200 Hz were studied, with a range of carrier rates up to 1200 Hz. It was found that all but one subject could consistently rank 150- and 200-Hz modulated stimuli by modulation frequency when the carrier rate was more than 800 Hz, but for lower carrier rates the ranking was greatly affected by the harmonic relationship between carrier and modulation frequency. Pitch matching experiments showed that the subjects generally considered the modulated stimuli to be equal in pitch to unmodulated stimuli with rates the same as, or somewhat higher than, the modulation frequency. The results showed that the "pitch" of pulsatile electrical stimulation resulting from periodicities in the time structure of the electrical stimulus has similarities to the "pitch" observed for temporal patterns in acoustic stimulation such as amplitude-modulated noise. There were some differences, however, which may be attributable at least in part to the physiological response differences for electric and acoustic stimulation.