Auditory detection and discrimination in deaf cats: psychophysical and neural thresholds for intracochlear electrical signals.

More than 30,000 hearing-impaired human subjects have learned to use cochlear implants for speech perception and speech discrimination. To understand the basic mechanisms underlying the successful application of contemporary speech processing strategies, it is important to investigate how complex electrical stimuli delivered to the cochlea are processed and represented in the central auditory system. A deaf animal model has been developed that allows direct comparison of psychophysical thresholds with central auditory neuronal thresholds to temporally modulated intracochlear electrical signals in the same animals. Behavioral detection thresholds were estimated in neonatally deafened cats for unmodulated pulse trains (e.g., 30 pulses/s or pps) and sinusoidal amplitude-modulated (SAM) pulse trains (e.g., 300 pps, SAM at 30 Hz; 300/30 AM). Animals were trained subsequently in a discrimination task to respond to changes in the modulation frequency of successive SAM signals (e.g., 300/8 AM vs. 300/30 AM). During acute physiological experiments, neural thresholds to pulse trains were estimated in the inferior colliculus (IC) and the primary auditory cortex (A1) of the anesthetized animals. Psychophysical detection thresholds for unmodulated and SAM pulse trains were virtually identical. Single IC neuron thresholds for SAM pulse trains showed a small but significant increase in threshold (0.4 dB or 15.5 microA) when compared with thresholds for unmodulated pulse trains. The mean difference between psychophysical and minimum neural thresholds within animals was not significant (mean = 0.3 dB). Importantly, cats also successfully discriminated changes in the modulation frequencies of the SAM signals. Performance on the discrimination task was not affected by carrier rate (100, 300, 500, 1,000, or 1,500 pps). These findings indicate that 1) behavioral and neural response thresholds are based on detection of the peak pulse amplitudes of the modulated and unmodulated signals, and 2) discrimination of successive SAM pulse trains is based on temporal resolution of the envelope frequencies. Overall, our animal model provides a robust framework for future studies of behavioral discrimination and central neural temporal processing of electrical signals applied to the deaf cochlea by a cochlear implant.

Responses of inferior colliculus neurons to amplitude-modulated intracochlear electrical pulses in deaf cats.

Current cochlear prostheses use amplitude-modulated pulse trains to encode acoustic signals. In this study we examined the responses of inferior colliculus (IC) neurons to sinusoidal amplitude-modulated pulses and compared the maximum unmodulated pulse rate (Fmax) to which they responded with the maximum modulation frequency (maxFm) that they followed. Consistent with previous results, responses to unmodulated pulses were all low-pass functions of pulse rate. Mean Fmax to unmodulated pulses was 104 pulses per second (pps) and modal Fmax was 60 pps. Above Fmax IC neurons ceased responding except for an onset burst at the beginning of the stimulus. However, IC neurons responded to much higher pulse rates when these pulses were amplitude modulated; 74% were relatively insensitive to carrier rate and responded to all modulated carriers including those exceeding 600 pps. In contrast, the responses of these neurons (70%) were low-pass functions of modulation frequency, and the remaining (30%) had band-pass functions with a maxFm of 42 and 34 Hz, respectively. Thus temporal resolution of IC neurons for modulated frequencies is significantly lower than that for unmodulated pulses. These two measures of temporal resolution (Fmax and maxFm) were uncorrelated (r(2) = 0.101). Several parameters influenced the amplitude and temporal structure of modulation responses including modulation depth, overall intensity and modulation-to-carrier rate ratio. We observed distortions in unit responses to amplitude-modulated signals when this ratio was 1/4 to 1/6. Since most current cochlear implant speech processors permit ratios that are significantly greater than this, severe distortion and signal degradation may occur frequently in these devices.

Electrical cochlear stimulation in the deaf cat: comparisons between psychophysical and central auditory neuronal thresholds.

Cochlear prostheses for electrical stimulation of the auditory nerve ("electrical hearing") can provide auditory capacity for profoundly deaf adults and children, including in many cases a restored ability to perceive speech without visual cues. A fundamental challenge in auditory neuroscience is to understand the neural and perceptual mechanisms that make rehabilitation of hearing possible in these deaf humans. We have developed a feline behavioral model that allows us to study behavioral and physiological variables in the same deaf animals. Cats deafened by injection of ototoxic antibiotics were implanted with either a monopolar round window electrode or a multichannel scala tympani electrode array. To evaluate the effects of perceptually significant electrical stimulation of the auditory nerve on the central auditory system, an animal was trained to avoid a mild electrocutaneous shock when biphasic current pulses (0.2 ms/phase) were delivered to its implanted cochlea. Psychophysical detection thresholds and electrical auditory brain stem response (EABR) thresholds were estimated in each cat. At the conclusion of behavioral testing, acute physiological experiments were conducted, and threshold responses were recorded for single neurons and multineuronal clusters in the central nucleus of the inferior colliculus (ICC) and the primary auditory cortex (A1). Behavioral and neurophysiological thresholds were evaluated with reference to cochlear histopathology in the same deaf cats. The results of the present study include: 1) in the cats implanted with a scala tympani electrode array, the lowest ICC and A1 neural thresholds were virtually identical to the behavioral thresholds for intracochlear bipolar stimulation; 2) behavioral thresholds were lower than ICC and A1 neural thresholds in each of the cats implanted with a monopolar round window electrode; 3) EABR thresholds were higher than behavioral thresholds in all of the cats (mean difference = 6.5 dB); and 4) the cumulative number of action potentials for a sample of ICC neurons increased monotonically as a function of the amplitude and the number of stimulating biphasic pulses. This physiological result suggests that the output from the ICC may be integrated spatially across neurons and temporally integrated across pulses when the auditory nerve array is stimulated with a train of biphasic current pulses. Because behavioral thresholds were lower and reaction times were faster at a pulse rate of 30 pps compared with a pulse rate of 2 pps, spatial-temporal integration in the central auditory system was presumably reflected in psychophysical performance.

Behavioral and neurophysiological thresholds for electrical cochlear stimulation in the deaf cat.

Psychophysical detection thresholds for unmodulated electrical pulse trains or for sinusoidally amplitude-modulated (SAM) pulse trains were estimated in deaf juvenile cats using a conditioned avoidance paradigm. Biphasic current pulses (0.2 ms/phase) were delivered by scala tympani electrodes consisting of 4-8 electrode contacts driven as bipolar pairs. Electrical auditory brainstem response (EABR) thresholds were obtained periodically, and at the conclusion of behavioral training, response thresholds were obtained for neurons in the inferior colliculus (IC) and the primary auditory cortex (A1) in acute physiological experiments in the same animals. The results of the study include: (1) detection thresholds for unmodulated pulse trains and for SAM pulse trains were virtually identical; (2) EABR thresholds and behavioral thresholds were significantly correlated, although EABR thresholds consistently overestimated behavioral thresholds; (3) the lowest thresholds in the IC and the A1 were significantly correlated with behavioral thresholds, and (4) mean lowest thresholds in the IC and the A1 were essentially the same as the mean psychophysical detection threshold in the trained deaf cats.

Temporal properties of chronic cochlear electrical stimulation determine temporal resolution of neurons in cat inferior colliculus.

As cochlear implants have become increasingly successful in the rehabilitation of adults with profound hearing impairment, the number of pediatric implant subjects has increased. We have developed an animal model of congenital deafness and investigated the effect of electrical stimulus frequency on the temporal resolution of central neurons in the developing auditory system of deaf cats. Maximum following frequencies (Fmax) and response latencies of isolated single neurons to intracochlear electrical pulse trains (charge balanced, constant current biphasic pulses) were recorded in the contralateral inferior colliculus (IC) of two groups of neonatally deafened, barbiturate-anesthetized cats: animals chronically stimulated with low-frequency signals (< or = 80 Hz) and animals receiving chronic high-frequency stimulation (> or = 300 pps). The results were compared with data from unstimulated, acutely deafened and implanted adult cats with previously normal hearing (controls). Characteristic differences were seen between the temporal response properties of neurons in the external nucleus (ICX; approximately 16% of the recordings) and neurons in the central nucleus (ICC; approximately 81% of all recordings) of the IC: 1) in all three experimental groups, neurons in the ICX had significantly lower Fmax and longer response latencies than those in the ICC. 2) Chronic electrical stimulation in neonatally deafened cats altered the temporal resolution of neurons exclusively in the ICC but not in the ICX. The magnitude of this effect was dependent on the frequency of the chronic stimulation. Specifically, low-frequency signals (30 pps, 80 pps) maintained the temporal resolution of ICC neurons, whereas higher-frequency stimuli significantly improved temporal resolution of ICC neurons (i.e., higher Fmax and shorter response latencies) compared with neurons in control cats. Furthermore, Fmax and latencies to electrical stimuli were not correlated with the tonotopic gradient of the ICC, and changes in temporal resolution following chronic electrical stimulation occurred uniformly throughout the entire ICC. In all three experimental groups, increasing Fmax was correlated with shorter response latencies. The results indicate that the temporal features of the chronically applied electrical signals critically influence temporal processing of neurons in the cochleotopically organized ICC. We suggest that such plastic changes in temporal processing of central auditory neurons may contribute to the intersubject variability and gradual improvements in speech recognition performance observed in clinical studies of deaf children using cochlear implants.

Functional organization of spectral receptive fields in the primary auditory cortex of the owl monkey.

Recent experiments in the cat have demonstrated that several response parameters, including frequency tuning, intensity tuning, and FM selectivity, are spatially segregated across the isofrequency axis. To investigate whether a similar functional organization exists in the primate, we have studied the spatial distribution of pure-tone receptive field parameters across the primary auditory cortex (AI) in six owl monkeys (Aotus trivirgatus). The distributions of binaural interaction types and onset latency were also examined. Consistent with previous studies, the primary auditory cortex contained a clear cochleotopic organization. We demonstrate here that several other properties of the responses to tonal stimuli also showed nonrandom spatial distributions that were largely independent from each other. In particular, the sharpness of frequency tuning to pure tones, intensity tuning and sensitivity, response latency, and binaural interaction types all showed spatial variations that were independent from the representation of characteristic frequency and from each other. Statistical analysis confirmed that these organizations did not reflect random distributions. The overall organizational pattern of overlaying but independent functional maps that emerged was quite similar to that seen in AI of cats and, in general, appears to reflect a fundamental organization principle of primary sensory cortical fields.

Acoustic pursuit of invisible moving targets by cats.

Head movements evoked by an invisible acoustic target were used as a metric to analyze localization of moving sources of sound in naive cats. The target was presented in the lateral sound field and moved along an arc at constant angular speeds. Head-movement trajectories were characterized by a large-magnitude orienting component that undershot the target, and a tracking component elicited by the target during acoustic pursuit. The tracking component was characterized by a succession of stepwise head movements that maintained a relatively close alignment of the median plane of the head with the moving acoustic target.

Contribution of auditory cortex to acoustical orientation in cats under conditions of discordant auditory reafference.

Head-orienting responses (ORs) evoked by a stationary source of sound typically terminate in small undershoots in normal hearing cats or in large undershoots (hypometria) if the auditory cortex is ablated bilaterally. In the present study, ORs executed by cats were studied using a procedure in which the OR produced an isogonal rotation of the sound source, i.e., response-produced change (reafference) in the acoustic stimulus was distorted. Under this condition (discordant auditory reafference), ORs terminated in large overshoots (hypermetria) in the normal hearing cats. This result indicates that experimental distortion of response-produced auditory feedback resulted in an "on-line" modification of ORs by the normal hearing cats. In the cats with auditory cortex ablated, ORs terminated in large undershoots (hypometria), suggesting that auditory cortex is a necessary component of the central auditory system for processing reafferent acoustic stimuli that normally occur during head rotation in a sound field.

Effects of bilateral and unilateral ablation of auditory cortex in cats on the unconditioned head orienting response to acoustic stimuli.

1. Reflexive head orienting responses (ORs) elicited by bursts of wide-band noise were investigated in cats after bilateral or unilateral ablation of the auditory cortex, and the cats' performance was compared with that of control cats. The OR was used as an indication of ability to orient toward the azimuthal direction of a source of sound. 2. To adequately test this ability, a unique combination of stimulus duration and position of the sound source was selected on each trial. Stimulus durations (0.1, 0.3, and 1.5 s) were selected so that the offset of a burst of noise occurred before, during, or after an OR. The stimuli were produced from speakers positioned approximately at the interaural horizontal plane within each quadrant of a cat's auditory field. The ORs were recorded on moving film and analyzed quantitatively. 3. In the control cats, the trajectory of the OR was characterized by a saccadic profile (rapid steplike movement, monophasic velocity, and biphasic acceleration). The accuracy of the OR varied directly with stimulus duration, suggesting that the response was modified by auditory feedback produced by a head movement during the stimulus. Corrective responses executed during long-duration (1.5 s) stimuli reduced residual mean error to < 7 degrees in each of the control animals. The mean error in orientation was smaller for sources located in the frontal sound field than for sources located behind the coronal plane the head (> 90 degrees). When brief (0.1 s) stimuli were presented behind the head, the cats confused back with front directions on most of the trials. 4. Compared with performance in the control cats, bilateral destruction of the auditory geniculocortical system severely impaired a cat's ability to orient consistently and accurately toward a source of sound. Latencies to the onset of ORs were increased, the magnitudes of ORs were reduced, average error in orienting to a sound source was larger under every stimulus duration-source position combination, relatively few corrective responses were executed, and residual mean error was significantly elevated (bilateral = 28.1 degrees; control = 3.1 degrees). Several animals with bilateral lesions also made vertical errors in orienting to azimuthal sources of sound. 5. However, in the bilateral lesion group, ORs were initiated in the correct right or left direction; and, rather than eliminating accurate responses altogether, the lesions reduced the probability of their occurrence. Furthermore, the saccadic profile of the response was preserved, providing evidence that the motor control system for the OR was not perturbed by the bilateral lesions.(ABSTRACT TRUNCATED AT 400 WORDS)

Functional development of mechanoreceptive neurons innervating the glabrous skin in postnatal kittens.

We studied single units innervating the glabrous forepaw skin of 35 domestic kittens ranging in age from 1 to 52 postnatal days. There aspects of coding were emphasized: (a) size and force thresholds of receptive fields, (b) time course of recovery between stimulus presentations, and (c) electrical conduction properties of the afferent nerve fibers. Receptive field (RF) size and force thresholds were (a) positively correlated with age for palmar but not digital RFs, and (b) were significantly larger on palm than on digits. Unit responsiveness was highly dependent on intertrial interval, complete recovery requiring at least 30 sec. Conduction velocity increased more rapidly than nerve fiber length, thus conduction time decreased with age. Refractory period decreased with age, but the conduction velocities of sequential spikes were proportional, regardless of age. These changes which we observed can more readily be ascribed to alterations of the mechanical properties of skin and conduction properties of nerve fibers than to changes in the coding mechanisms themselves.

Response of unmyelinated (C) polymodal nociceptors to thermal stimuli applied to monkey's face.

1. The response of C polymodal nociceptors to thermal and mechanical stimuli applied to the monkey's face was recorded extracellulary in the trigeminal ganglion in rhesus monkeys anesthetized with sodium pentobarbital. Conduction velocities, determined from electrical stimulation of receptive fields (RFs), were in the range for unmyelinated C fibers (mean=0.82 m/s, n=20; SD=+/-0.17). With two exceptions cutaneous RFs were single spots (median=2 mm2; n=37) and usually were identical for thermal and mechanical stimuli. The median force threshold for the sample of units was 1.2 g (von Frey technique; n = 39; range = 0.07-8.5 g). 2. Discharges to thermal stimuli were investigated with a feedback-controlled contact thermode which permitted temperature changes less than or equal 12.0 degrees C/s. Thermal thresholds ranged from 38 degree to 49 degree C (median=46 degrees C; n=37), and maximum discharge frequencies were obtained in the noxious heat range (45-55 degrees C). For a graded series of 5 s duration stimuli from an adapting temperature of 35 degrees C, the number of impulses increased as a monotonic function of stimulus intensity over the range from threshold temperature to 50-53 degrees C. Many stimulus-response functions were positively accelerated, and linear regression analyses showed that most units examined were best fit by nonlinear functions. 3. The typical pattern of activity to 5 s duration temperature shifts into the noxious heat range was a short accelerating burst of impulses followed by deceleration to a lower rate of discharge prior to termination of the stimulus. The temporal profile of the discharge of impulses was virtually identical at different adapting temperatures. In units tested with 30 s duration stimuli at 2-6 degrees C above threshold, the mean frequency of discharge during the final 25 s was 1.46 impulses/s (n=6; SD=+/-0.89). 4. Application of noxious heat stimuli a few degrees above threshold temperature typically sensitized or enhanced the response of the unit to subsequent application of heat stimuli. The signs of sensitization consisted of a decrease in threshold temperature, increased frequency of discharge, decreased latency to the first impulse, and afterdischarges. Units failed to respond throughout the duration of 30 s stimuli if the final temperature exceeded 50 degrees C. Depressed responses were sometimes produced by application of intense (greater than or equal 55 degrees C) stimuli, presumably as a result of partial inactivation of the receptor. 5. In a correlative analysis, the latency and pattern of discharge in a sample of units were compared with escape responses in two monkeys to temperature shifts into the noxious heat range (49 and 51 degrees C). The analysis revealed that the discharge of C polymodal nociceptors alone cannot account for fast escape responses, but the discharge may contribute to escape responses which occur more than 3.5 s after the onset of stimulation.

Diversity of coding profiles of mechanoreceptors in glabrous skin of kittens.

We examined stimulul-response (S-R) profiles of 35 single mechanoreceptive afferent units having small receptive fields in glabrous forepaw skin of 24 anesthetized domestic kittens. Single unit activity was recorded with tungsten microelectrodes from cervical dorsal root ganglia. The study was designed to be as quantitatively descriptive as possible. We indented each unit's receptive field with a broad battery of simple, carefully controlled stimuli whose major parameters, including amplitude, velocity, acceleration, duration, and interstimulus interval were systematically varied. Stimuli were delivered by a small probe driven by a feedback-controlled axial displacement generator. Single unit discharge data were analyzed by a variety of direct and derived measures including dot patterns, peristimulus histograms, instantaneous and mean instantaneous firing rates, tuning curves, thresholds for amplitude and velocity, adaptation rates, dynamic and static sensitivities, and others. We found that with respect to any of the S-R transactions examined, the properties of our sample of units were continuously and broadly distributed. Any one unit might exhibit either a slow or rapid rate of adaptation, or might superficially appear to preferentially code a single stimulus parameter such as amplitude or velocity. But when the entire range of responsiveness of units to the entire stimulus battery was surveyed by a variety of analytic techniques, we were unable to find any justifiable basis for designation of discrete categories of S-R profiles. Intermediate response types were always found, and in general, all units were both broadly tuned and capable of responding to integrals of several stimulus parameters, our data argue against the usefulness of evaluating a unit's S-R coding capabilities by means of a limited ste of stimulation of response analysis procedures.