Mapping the VIIIth cranial nerve by electrical stimulation: methods for differentiating auditory from vestibular responses.

HYPOTHESIS: The goal of this study was to map the VIIIth cranial nerve by electrical stimulation. Specifically, the authors sought to 1) characterize auditory and vestibular evoked responses elicited by electrical stimuli delivered directly to the exposed surface of the VIIIth cranial nerve and 2) compare electrically evoked responses elicited in brainstem nuclei with extracranially recorded far-field potentials. BACKGROUND: Intraoperative monitoring of auditory brainstem responses is useful during cerebellopontine angle surgery. Identification of the vestibular portion of the VIIIth cranial nerve, which traditionally has been performed by physical characteristics and some electrophysiologic properties, is important because the vestibular subdivision in humans is indistinct in approximately 25% of cases. Positive identification of evoked responses emanating from the vestibular nerve would constitute a marked improvement over existing intraoperative techniques that use acoustic stimuli only. METHODS: Experiments were performed on 12 anesthetized cats. Electrical pulse stimuli were delivered using a bipolar electrode placed directly on the surface of the exposed VIIIth cranial nerve at several sites. Computer-averaged evoked responses were recorded from far-field electrodes placed on the scalp and from near-field electrodes stereotaxically positioned in or near the inferior colliculus and abducens nucleus. RESULTS: Latencies and morphologies of waves recorded in brainstem nuclei were compared with those of waves recorded extracranially. Direct electrical stimulation of the cochlear nerve elicited a four-wave, auditory brainstem response-like extracranial response, strong activity in the inferior colliculus, and weak activity in the abducens nucleus. Direct stimulation of the vestibular nerve produced a two-wave extracranial response, weak inferior colliculus activity, and strong abducens activation. Stimulation at the border of the cochlear and vestibular nerves produced intermediate responses that possessed both cochlear and vestibular characteristics. CONCLUSION: Direct electrical stimulation of the cochlear and vestibular subdivisions elicits evoked responses with distinctly different wave morphologies. Obtaining electrically evoked responses intraoperatively is feasible and may be of substantial value in the unambiguous identification of VIIIth cranial nerve subdivisions.

The development of the middle ear in neonatal chinchillas II. Two weeks to adulthood.

Studies of auditory function in the human neonate indicate adult-like hearing sensitivity, mature cochlear function and well-developed responses in the auditory pathway. Paradoxically, measurements of middle ear function are characterized by responses that would be interpreted as abnormal in older subjects. Consequently, there is not an accepted clinical test for middle ear disease in the newborn population. Like human neonates, chinchillas have normal hearing sensitivity at birth, but middle ear function tested by multifrequency tympanometry is abnormal compared to the adult. A previous study from our laboratory indicated that the newborn chinchilla middle ear is free of mesenchyme and other debris. Over the first 2 weeks of life there were no significant changes in tympanic membrane thickness and diameter, tympanic membrane to promontory distance and stapes footplate length. There were small changes in mastoid bulla area and perimeter and in mastoid bulla bone thickness. The most striking difference between the newborn and adult temporal bone was in bone composition, the newborn bone having a less dense, spongy appearance. Impedance characteristics of the newborn chinchilla ear, measured by multifrequency tympanometry, were abnormal relative to adult animals and did not change over the first 2 weeks of life. This investigation is an extension of the previous study, designed to better understand the relationship between middle ear function, hearing sensitivity and the structural changes of the newborn chinchilla middle ear. Twenty animals, aged 2-8 weeks, were studied. Additional adult animals were used as controls. Middle ear function was assessed by a wideband reflectance impedance system. Hearing sensitivity was measured by auditory brainstem response in 2- and 8-week-old animals. Structural characteristics of the temporal bone were analyzed using histopathologic preparations. There was an orderly progression in middle ear impedance and reflectance characteristics as the chinchilla ear matured from 2 to 8 weeks of age. At 8 weeks of age, impedance and reflectance patterns approached, but did not match, those of the adult animal. Hearing sensitivity was unchanged throughout this maturational period. Finally, histological analysis demonstrated no age-related changes in distance from the tympanic membrane (TM) to the promontory and in stapes footplate length. There was a small significant decrease in the TM thickness from 2 weeks to adulthood. The most significant developmental changes were a reduction in mastoid bone thickness and concomitant increases in the perimeters and areas of the middle ear and posterior bulla.

Electrical stimulation of the auditory nerve. III. Response initiation sites and temporal fine structure.

Latency, temporal dispersion and input-output characteristics of auditory nerve fiber responses to electrical pulse trains in normal and chronically deafened cat ears were classified and tentatively associated with sites where activity is initiated. Spikes occurred in one or more of four discrete time ranges whose endpoints overlapped partially. A responses had latencies <0.44 ms, exhibited asymptotic temporal dispersion of 8-12 micros and possessed an average dynamic range of 1.2 dB for 200 pulses/s (pps) pulse trains. They likely originated from central processes of spiral ganglion cells. B(1) and B(2) responses (0.45-0.9 ms, 25-40 micros, 1.9 dB) likely stemmed from activity at myelinated and unmyelinated peripheral processes, respectively. C100 micros) likely originated from direct stimulation of inner hair cells, and D8 dB) arose from propagating traveling waves possibly caused by electrically induced motion of outer hair cells. C and D responses were recorded only in acoustically responsive ears. Mean latencies of spikes in all time ranges usually decreased with intensity, and activity at two or even three discrete latencies was often observed in the same spike train. Latency shifts from one discrete time range to another often occurred as intensity increased. Some shifts could be attributed to responses to the opposite-polarity phase of the biphasic pulse. In these cases, temporal dispersion and dynamic range were approximately equal for activity at each latency. A second type of latency shift was also often observed, in which responses at each latency exhibited dissimilar temporal dispersion and dynamic range. This behavior was attributed to a centralward shift in the spike initiation site and it occurred for monophasic as well as biphasic signals. Several fibers exhibited dual latency activity with a 40-90 micros time difference between response peaks. This may have stemmed from spike initiation at nodes on either side of the cell body. Increasing the stimulus pulse rate to 800-1000 pps produced small increases in temporal dispersion and proportionate increases in asymptotic discharge rate and dynamic range, but thresholds did not improve and slopes of rate-intensity functions (in spikes/s/dB) did not change. Responses to high-rate stimuli also exhibited discrete latency increases when discharge rates exceeded 300-400 spikes/s. Spike by spike latencies in these cases depended strongly on the discharge history. Implications for high-rate speech processing strategies are discussed.

Stochastic properties of cat auditory nerve responses to electric and acoustic stimuli and application to intensity discrimination.

Statistical properties of electrically stimulated (ES) and acoustically stimulated (AS) auditory nerve fiber responses were assessed in undeafened and short-term deafened cats, and a detection theory approach was used to determine fibers' abilities to signal intensity changes. ES responses differed from AS responses in several ways. Rate-level functions were an order of magnitude steeper, and discharge rate normally saturated at the stimulus pulse rate. Dynamic ranges were typically 1-4 dB for 200 pps signals, as compared with 15-30 dB for AS signals at CF, and they increased with pulse rate without improving threshold or changing absolute rate-level function slopes. For both ES and AS responses, variability of spike counts elicited by repeated trials increased with level in accord with Poisson-process predictions until the discharge rate exceeded 20-40 spikes/s. AS variability continued increasing monotonically at higher discharge rates, but more slowly. In contrast, maximum ES variability was usually attained at 100 spikes/s, and at higher discharge rates variability reached a plateau that was either maintained or decreased slightly until discharge rate approached the stimulus pulse rate. Variability then decreased to zero as each pulse elicited a spike. Increasing pulse rate did not substantially affect variability for rates up to 800 pps; rather, higher pulse rates simply extended the plateau region. Spike count variability was unusually high for some ES fibers. This was traced to response nonstationarities that stemmed from two sources, namely level-dependent fluctuations in excitability that occurred at 1-3 s intervals and, for responses to high-rate, high-intensity signals, fatigue that arose when fibers discharged at their maximum possible rates. Intensity discrimination performance was assessed using spike count as the decision variable in a simulated 2IFC task. Neurometric functions (percent correct versus intensity difference) were obtained at several levels of the standard (I), and the intensity difference (delta I) necessary for 70% correct responses was estimated. AS Weber fractions (10 log delta I/I) averaged +0.2 dB (delta IdB = 3.1 dB) for 50 ms tones at CF. ES Weber fractions averaged -12.8 dB (delta IdB = 0.23 dB) for 50 ms, 200 pps signals, and performance was approximately constant between 100 and 1000 pps. Intensity discrimination by single cells in ES conditions paralleled human psychophysical performance for similar signals. High ES sensitivity to intensity changes arose primarily from steeper rate-level functions and secondarily from reduced spike count variability.

Effect of stress-related hormones on inner ear fluid homeostasis and function.

HYPOTHESIS: Induction of suprathreshold levels of stress-related hormone by systemic administration of epinephrine can change inner ear fluid homeostasis and function. BACKGROUND: Meniere's disease is frequently associated with high levels of anxiety and other forms of psychological disturbance. Most clinicians agree that emotional stress or severe anxiety can precipitate relapse or aggravate the symptoms. In general, it is known that stress-related hormones such as epinephrine, norepinephrine, vasopressin, aldosterone, and cortisol are released into systemic circulation in response to stress. Significantly higher levels of plasma norepinephrine and vasopressin in patients with Meniere's disease have been reported. METHODS: Concentrations of sodium and potassium in perilymph were measured by a flame photometer after systemic infusion of epinephrine (6.3 microg/min for 3 hours). Control animals were treated with equal volumes of 0.9% physiologic saline. Compound action potentials (CAP) elicited by brief tone bursts were measured before and 3 hours after the infusion of epinephrine. For chronic studies, epinephrine (10 microg/d/kg) was given by osmotic pump implanted subcutaneously for 1, 2, 3, and 4 weeks, respectively. Click- and tone-evoked auditory brain responses (ABRs) were measured at 1, 2, 3, and 4 weeks after epinephrine administration. RESULTS: Concentrations of sodium and potassium increased significantly in perilymph (p < 0.001 and p < 0.01) after epinephrine infusion over controls. The osmolality increased significantly in serum and perilymph after epinephrine infusion. The CAP threshold was significantly elevated at all frequencies. The shift of the CAP threshold caused by epinephrine tended to be larger at higher frequencies. In chronic studies, epinephrine administration caused a transient 20 to 45 dB threshold shift that increased with time and was relatively constant across frequency. CONCLUSIONS: There is good evidence to suggest that stress-related hormones such as epinephrine can alter inner ear fluid homeostasis and auditory function. This study confirmed this hypothesis and illuminated the processes of alteration by demonstrating specific changes in perilymph composition and auditory function.

Physiologic identification of eighth nerve subdivisions: direct recordings with bipolar and monopolar electrodes.

The purpose of this study was to determine stimulation and recording parameters that maximize differences in evoked responses recorded between the cochlear nerve and the surrounding tissues. Click-evoked potentials were obtained using monopolar and bipolar recording electrodes placed directly on the exposed eighth nerve of anesthetized cats. Responses were compared as stimulus intensity, electrode location, and bipolar electrode orientation and interelectrode spacing were systematically varied. Wave amplitudes increased monotonically with intensity for both monopolar and bipolar configurations, but bipolar configurations exhibited greater selectivity in differentiating cochlear from vestibular subdivisions. The optimal stimulus intensity was 70 to 80 dB peak sound pressure level (pSPL). Monopolar recordings were often confounded by activity originating at remote sites, typically the cochlear nucleus and (for recording sites on the vestibular nerve) the cochlear nerve. Bipolar response amplitudes increased with interelectrode spacing and were largest when electrodes were oriented parallel to the long axis of the nerve. Extrapolation of empirical data indicated that amplitudes of bipolar responses would be maximal at an electrode separation of 7.5 mm. Cochlear nerve conduction velocity, calculated from wave latencies at each of the two monopolar electrodes, was 11.6 +/- 1.6 m/sec.

A stochastic model of the electrically stimulated auditory nerve: single-pulse response.

Most models of neural response to electrical stimulation, such as the Hodgkin-Huxley equations, are deterministic, despite significant physiological evidence for the existence of stochastic activity. For instance, the range of discharge probabilities measured in response to single electrical pulses cannot be explained at all by deterministic models. Furthermore, there is growing evidence that the stochastic component of auditory nerve response to electrical stimulation may be fundamental to functionally significant physiological and psychophysical phenomena. In this paper we present a simple and computationally efficient stochastic model of single-fiber response to single biphasic electrical pulses, based on a deterministic threshold model of action potential generation. Comparisons with physiological data from cat auditory nerve fibers are made, and it is shown that the stochastic model predicts discharge probabilities measured in response to single biphasic pulses more accurately than does the equivalent deterministic model. In addition, physiological data show an increase in stochastic activity with increasing pulse width of anodic/cathodic biphasic pulses, a phenomenon not present for monophasic stimuli. These and other data from the auditory nerve are then used to develop a population model of the total auditory nerve, where each fiber is described by the single-fiber model.

A stochastic model of the electrically stimulated auditory nerve: pulse-train response.

The single-pulse model of the companion paper [1] is extended to describe responses to pulse trains by introducing a phenomenological refractory mechanism. Comparisons with physiological data from cat auditory nerve fibers are made for pulse rates between 100 and 800 pulses/s. First, it is shown that both the shape and slope of mean discharge rate curves are better predicted by the stochastic model than by the deterministic model. Second, while interpulse effects such as refractory effects do indeed increase the dynamic range at higher pulse rates, both the physiological data and the model indicate that much of the dynamic range for pulse-train stimuli is due to stochastic activity. Third, it is shown that the stochastic model is able to predict the general magnitude and behavior of variance in discharge rate as a function of pulse rate, while the deterministic model predicts no variance at all.

Electrical stimulation of the auditory nerve: II. Effect of stimulus waveshape on single fibre response properties.

To investigate the generation of action potentials by electrical stimulation we studied the response of auditory nerve fibres (ANFs) to a variety of stimulus waveforms. Current pulses were presented to longitudinal bipolar scala tympani electrodes implanted in normal and deafened cochleae. Capacitively coupled monophasic current pulses evoked single ANF responses that were more sensitive to one phase (the 'excitatory' phase) than the other. Anodic pulses produced a significantly shorter mean latency compared with cathodic pulses, indicating that their site for spike initiation is located more centrally along the ANF. The fine temporal structure of ANF responses to biphasic pulses appeared similar to that evoked by monophasic pulses. An excitatory monophasic pulse evoked a significantly lower threshold than a biphasic current pulse having the same polarity and duration leading phase, i.e. the addition of a second phase leads to an increase in threshold. Increasing the temporal separation of the two phases of a biphasic pulse resulted in a moderate reduction in threshold which approached that of an excitatory monophasic pulse for interphase gaps > 100 micros. Greater threshold reductions were observed with narrower current pulses. There was a systematic reduction in threshold with increasing pulse width for biphasic current pulses, reflecting the general charge-dependent properties of ANFs for narrow pulse widths. Chopped biphasic current pulses, which uniformly delivered multiple packets of charge (2 x 30 micros, 3 x 20 micros or 6 x 10 micros) with the same polarity over a 120 micros period, followed by a similar series in the reverse polarity, demonstrated the ability of the neural membrane to integrate sub-threshold packets of charge to achieve depolarisation. Moreover, thresholds for these current pulses were approximately 1.5 dB lower than 60 micros/phase biphasic current pulses with no interphase gap. Finally, stimulation using charge-balanced triphasic and asymmetric current pulses produced systematic changes in threshold and latency consistent with the charge-dependent properties of ANFs. These findings provide insight into the mechanisms underlying the generation of action potentials using electrical stimuli. Moreover, a number of these novel stimuli may have potential clinical application.

Electrical stimulation of the auditory nerve. I. Correlation of physiological responses with cochlear status.

The purpose of the present study was to evaluate evoked potential and single fibre responses to biphasic current pulses in animals with varying degrees of cochlear pathology, and to correlate any differences in the physiological response with status of the auditory nerve. Six cats, whose cochleae ranged from normal to a severe neural loss (< 5% spiral ganglion survival), were used. Morphology of the electrically evoked auditory brainstem response (EABR) was similar across all animals, although electrophonic responses were only observed from the normal animal. In animals with extensive neural pathology, EABR thresholds were elevated and response amplitudes throughout the dynamic range were moderately reduced. Analysis of single VIIIth nerve fibre responses were based on 207 neurons. Spontaneous discharge rates among fibres depended on hearing status, with the majority of fibres recorded from deafened animals exhibiting little or no spontaneous activity. Electrical stimulation produced a monotonic increase in discharge rate, and a systematic reduction in response latency and temporal jitter as a function of stimulus intensity for all fibres examined. Short-duration current pulses elicited a highly synchronous response (latency < 0.7 ms), with a less well synchronized response sometimes present (0.7-1.1 ms). There were, however, a number of significant differences between responses from normal and deafened cochleae. Electrophonic activity was only present in recordings from the normal animal, while mean threshold, dynamic range and latency of the direct electrical response varied with cochlear pathology. Differences in the ability of fibres to follow high stimulation rates were also observed; while neurons from the normal cochlea were capable of 100% entrainment at high rates (600-800 pulses per second (pps)), fibres recorded from deafened animals were often not capable of such entrainment at rates above 400 pps. Finally, a number of fibres in deafened animals showed evidence of 'bursting', in which responses rapidly alternated between high entrainment and periods of complete inactivity. This bursting pattern was presumably associated with degenerating auditory nerve fibres, since it was not recorded from the normal animal. The present study has shown that the pathological response of the cochlea following a sensorineural hearing loss can lead to a number of significant changes in the patterns of neural activity evoked via electrical stimulation. Knowledge of the extent of these changes have important implications for the clinical application of cochlear implants.

Intensity discrimination as a function of stimulus level with electric stimulation.

Difference limens (DLs) for changes in electric current were measured from multiple electrodes in each of eight cochlear-implanted subjects. Stimuli were 200-microseconds/phase biphasic pulse trains delivered at 125 Hz in 300-ms bursts. DLs were measured with an adaptive three-alternative forced-choice procedure. Fixed-level psychometric functions were also obtained in four subjects to validate the adaptive DLs. Relative intensity DLs, specified as Weber fractions in decibels [10 log (delta I/I)] for standards above absolute threshold, decreased as a power function of stimulus intensity relative to absolute threshold [delta I/I = beta (I/I0) alpha] in the same manner as Weber fractions for normal acoustic stimulation reported in previous studies. Exponents (alpha) of the power function for electric stimulation ranged from -0.4 to -3.2, on average, an order of magnitude larger than exponents for acoustic stimulation, which range from -0.07 to -0.11. Normalization of stimulus intensity to the dynamic range of hearing resulted in Weber functions with similar negative slopes for electric and acoustic stimulation, corresponding to an 8-dB average improvement in Weber fractions across the dynamic range. Sensitivity to intensity change ¿10 log beta¿ varied from -0.42 to -13.5 dB compared to +0.60 to -3.34 dB for acoustic stimulation, but on average was better with electric stimulation than with acoustic stimulation. Psychometric functions for intensity discrimination yielded Weber fractions consistent with adaptive procedures and d' was a linear function of delta I. Variability among repeated Weber-fraction estimates was constant across dynamic range. Relatively constant Weber fractions across all or part of the dynamic range, observed in some subjects, were traced to the intensity resolution limits of individual implanted receiver/stimulators. DLs could not be accurately described by constant amplitude changes, expressed as a percentage of dynamic range ¿delta A(% DR)¿. Weber fractions from prelingually deafened subjects were no better or worse than those from postlingually deafened subjects. The cumulative number of discriminable intensity steps across the dynamic range of electric hearing ranged from as few as 6.6 to as many as 45.2. Physiologic factors that may determine important features of electric intensity discrimination are discussed in the context of a simple, qualitative, rate-based model. These factors include the lack of compressive cochlear preprocessing, the relative steepness of neural rate-intensity functions, and individual differences in patterns of neural survival.

Long-term adaptation in cat auditory-nerve fiber responses.

Driven responses of cat auditory-nerve fibers to long-duration characteristic-frequency (CF) tones could decrease substantially over time periods ranging from seconds to minutes. In extreme cases, the discharge rate could fall before the pre-stimulation spontaneous rate (SR). Reductions in response were characterized by two processes, each of which followed a decaying exponential function. long-term adaptation affects the discharge rate in the first several seconds following stimulus onset. The average amount in high-SR fibers was 42.5% for tones at 20-40 dB SL, and the mean time constant was 3.65 s. Long-term adaptation increased significantly with sensation level (SL, or level above threshold), decreased with SR, and was not significantly correlated with CF or fiber response threshold. Time constants did not depend on CF, SR, or SL. Very-long-term adaptation refers to further, smaller reductions in the discharge rate that accumulate over a period of minutes. Fiber responses formed two groups. The larger group adapted with a mean time constant of 45.22 s for CF tones at 20-40 dB SL, and the smaller group did not adapt over very long terms. Considerable variability in amounts of long-term and very-long-term effects do not arise from cochlear mechanics or middle ear muscle activity. No long-term effects were observed in responses of fibers directly stimulated by high-intensity electrical pulses present at rates up to 500/s through a cochlear implant. This suggests that the effects do not arise from fundamental differences in spike-generating properties of spiral ganglion cells. The data suggest that long-term adaptation may occur either when neurotransmitter utilization at inner hair cell synapses exceeds the rate at which it is replenished from global stores or uptake mechanisms, or which metabolic resources influencing neurotransmitter release become depleted. The neural data are related to perceptual findings in human listeners, in which unusually large amounts of tone decay may be observed at high frequencies, and they indicate that the perceptual effects originate peripherally.

Shapes of cat auditory nerve fiber tuning curves.

Tuning curves of auditory nerve fibers in normal-hearing cats were fitted by a computational model comprising four processes. One process accounts for sensitivity in tuning curve tails and consists of an approximation to bandpass filtering by extracochlear structures. The second and third processes describe passive and active components of basilar membrane (BM) mechanics, respectively. The former consists of a lowpass filter function, which provides baseline threshold sensitivity and filtering above characteristic frequency (CF), and the latter consists of a Gaussian that accounts for sharp tuning and high sensitivity around CF. A fourth process, modeled as a high-pass filter, was needed in many fits to account for breaks and plateaus in threshold sensitivity at frequencies above CF. The latter three processes operated on cochlear spatial coordinates rather than stimulus frequency. The four-process description closely accounted for shapes of most tuning curves. Tuning curve tails possessed minima at 40-80 dB SPL, and minima increased with fiber CF. High-frequency cutoffs of tail filters tended to increase with CF, but low-frequency cutoffs were generally constant across CF. Functions describing tails varied from ear to ear but behaved in a similar manner for fibers from a single ear. Passive components of BM resonances possessed baselines with sensitivities that decreased with CF and cutoff slopes that increased with CF. The magnitude of the active component increased smoothly with CF over an 80 + dB range, and its spatial extent was essentially constant at 1.5 mm or 6% of cochlear length regardless of gain magnitude, fiber CF, or threshold sensitivity. Tuning curves from fibers with high and medium spontaneous rates (SRs) and similar CFs had nearly identical shapes, with the sole difference being essentially constant differences in sensitivity across the entire excitatory frequency range. Tuning curve shapes from fibers with low SRs were more variable. These could either resemble those obtained from similarly-tuned fibers with higher SRs, or they could exhibit lower tip-to-tail ratios and reduced active component magnitudes. The latter were typically associated with low maximum discharge rates.

Selective degeneration of a putative cholinergic pathway in the chinchilla cochlea following infusion with ethylcholine aziridinium ion.

Ethylcholine aziridinium ion (AF64A) diluted in artificial perilymph, or artificial perilymph alone was infused into the cochlea of chinchillas. After a survival time of 7 days, the cochleas were fixed with aldehydes, post-fixed in osmium and embedded in epoxy resin for light and electron microscopy. The ultrastructure of the cochleas infused with artificial perilymph was normal. Infusion of 1 microM AF64A resulted in massive degeneration of the axons of the lateral efferent system, a putative cholinergic pathway that originates in the brainstem and terminates on dendrites of the spiral ganglion innervating cochlear inner hair cells. The axons and terminals of a second putative cholinergic pathway, the medial efferent system which terminates on the outer hair cells, were normal. Infusion of AF64A in a concentration of 10 microM resulted in significant pathology of cochlear and supporting cells as well as the loss of efferent terminals at both inner and outer hair cell regions. The results suggest that AF64A is a selective neurotoxin when used under low-dosage conditions, and that certain pathways may be more susceptible to the effects of AF64A than others. One interpretation of these findings is that lateral efferent axons may have a higher rate of high-affinity choline uptake than terminals of the medial efferent axons.

Coding of spectral fine structure in the auditory nerve. II: Level-dependent nonlinear responses.

Phase-locked discharge patterns of single cat auditory-nerve fibers were analyzed in response to complex tones centered at fiber characteristic frequency (CF). Signals were octave-bandwidth harmonic complexes defined by a center frequency F and an intercomponent spacing factor N, such that F/N was the fundamental frequency. Parameters that were manipulated included the phase spectrum, the number of components, and the intensity of the center component. Analyses employed Fourier transforms of period histograms to assess the degree to which responses were synchronized to the frequencies present in the acoustic stimulus. Several nonlinearities were observed in the response as intensity was varied between threshold and 80-90 dB SPL. Response nonlinearities were strong for all signals except those with random phase spectra. The most commonly observed nonlinearity was an emphasis of one or more stimulus components in the response. The degree of nonlinearity usually increased with intensity and signal complexity and decreased with fiber frequency selectivity. Half-wave rectification introduced synchronization to the missing fundamental. The strength of the response at the fundamental was related to stimulus crest factor. Signals with low center frequencies and high crest factors often elicited instantaneous discharge rates at the theoretical maximum of pi CF. This suggests that the probability of spike generation approaches one during high-amplitude waveform segments. Response nonlinearity was interpreted as arising from three sources, namely, cochlear mechanics, compression of instantaneous discharge rate, and saturation of average discharge rate. At near-threshold intensities, fibers with high spontaneous rates exhibited responses that were linear functions of stimulus waveshape, whereas fibers with low spontaneous spike rates produced responses that were best described in terms of an expansive nonlinearity.

Physiological and psychophysical correlates of temporal processes in hearing.

Discharges of auditory nerve fibers are synchronized to stimulus frequencies below 4-5 kHz. The phase-locking phenomenon has been studied in considerable detail in several animal species. Although strikingly close correspondences exist between phase-locking behavior in animals and human perceptual performance on certain tasks, there is still no clear evidence that the human brain actually bases perceptual decisions on temporally encoded frequency information. The alternative to temporal coding is rate-place coding, in which frequency is assigned on the basis of peaks in cochlear excitation patterns. This paper reviews pertinent physiological, psychophysical and modeling data in three classes of experiment whose results are explanable in terms of both rate-place and temporal processing of neural responses. The experiments deal with the pitch of complex tones, vowel identification, and pure-tone frequency discrimination. The data described here suggest that temporal models of frequency coding compete well with and in some cases offer a more parsimonious explanation of perceptual performance than rate-place codes do, particularly at low and middle frequencies. A potentially important implication of the analyses conducted here is that humans may not code frequency information in synchronized activity as well as other species. The data suggest that within limits the human ear is capable of using either temporal and rate-place frequency codes, and that the specific code employed by the perceptual processor is task-dependent.

Development of auditory-evoked potentials in the cat. I. Onset of response and development of sensitivity.

Auditory-evoked potentials, originating from the brain stem and the forebrain, were studied in 30 unanesthetized kittens during the first 3 months of postnatal life, and from a smaller set of animals before and after surgical exposure of their tympanic membranes. In intact animals, responses to 135-dB peak SPL clicks were first reliably discernible on the seventh postnatal day; when stimuli were presented directly to the exposed tympanic membrane, responses were observed several days earlier. Responses progressed through three stages during maturation: an early period of gross insensitivity during which responses are evoked only by high-intensity stimuli and whose response thresholds remain essentially constant (week 1); a middle period characterized by rapid acquisition of sensitivity to near-adult values (week 2); and a late period during which adult thresholds and latencies are acquired. A sequential stage model of threshold maturation is proposed, in which thresholds decline linearly during stage two and exponentially during stage three. It is hypothesized that mechanical reorganization of the cochlea during the first 2 to 3 postnatal weeks and development of the stria vascularis are primarily responsible for the linear stage, and that neural factors primarily underlie the exponential stage and account for the gradual acquisition of adult thresholds. Rates of maturation for brain stem responses are frequency dependent, with responses to high frequencies achieving adult thresholds earlier than those to low frequencies.

Development of auditory-evoked potentials in the cat. II. Wave latencies.

Brain stem and forebrain auditory-evoked potentials were studied parametrically during the first 90 postnatal days in unanesthetized kittens using tonal and click stimuli. This paper describes changes that occur in transmission time through the auditory pathway during development by analyses of the maturational time courses of latencies associated with waves of both auditory brain stem responses (ABR's) and late-occurring auditory-evoked potentials (AER's), recorded subdermally from the vertex. In response to click stimuli, ABR latencies were found to decay rapidly early in postnatal life and more slowly after the third postnatal week. Those trends were modeled as a two-stage sequential process, with a linear stage occurring between 7 and 18 postnatal days followed by an exponential stage during which adult latencies were achieved. AER latencies changes during development were less complicated, and followed a single-stage exponential time course. When threshold influences were taken into account--that is, when data were adjusted so that sensation level (SL) was constant across age--the latency-maturation curves associated with all ABR waves were adequately described by a single exponential, and latencies recorded from young animals were substantially shorter than latencies associated with the same aged animals when analyses were carried out with constant sound-pressure level (SPL) stimuli across age. In addition, the difference function, generated when isoasymptotic SPL and SL latency versus age functions were subtracted from one another, was also represented by an exponential curve, suggesting that at least two processes underlie the latency decay that occurs during postnatal development. Evoked responses to tonal stimuli throughout development were consistent with the basoapical developmental gradient that is observed anatomically.

Development of auditory-evoked potentials in the cat. III. Wave amplitudes.

Amplitudes of auditory-evoked brain stem response (ABR) and late-occurring auditory-evoked potential (AER) components were recorded from kittens between birth and 90 postnatal days. All ABR and AER wave amplitudes increased during the first postnatal month. Wave amplitudes exhibited nonmonotonic growth with increasing age, attaining a maximum at 40-60 days of age, after which amplitudes decreased. Amplitudes of waves originating in the auditory nerve matured somewhat faster than waves originating in the brain stem and forebrain, and the order in which waves reached maturity was roughly the reverse order of the latencies of their peaks. Input-output curves for ABR and AER waves displayed nonmonotonic behavior that varied as a function of postnatal age. Wave amplitudes recorded from adult cats increased between threshold and 70 dB SPL, then decreased between 70 and 100 dB SPL, and rapidly increased above 100 dB SPL. The intensity corresponding to the change from increasing to decreasing amplitudes was higher for younger animals and achieved adult values during the first postnatal month.

Coding of spectral fine structure in the auditory nerve. I. Fourier analysis of period and interspike interval histograms.

The temporal fine structure of discharge patterns of single auditory-nerve fibers in adult cats was analyzed in response to signals consisting of a variable number of equal-intensity, in-phase harmonics of a common low-frequency fundamental. Two analytic methods were employed. The first method considered Fourier spectra of period histograms based on the period of the fundamental, and the second method considered Fourier spectra of interspike interval histograms (ISIH's). Both analyses provide information about fiber tuning properties, but Fourier spectra of ISIH's also allow estimates to be made of the degree of resolution of individual stimulus components. At low intensities (within 20-40 dB of threshold), indices of synchronization to individual components of complex tones were similar to those obtained for pure tones. This was true even when fibers were capable of responding to several signal components simultaneously. Response spectra obtained at low intensities resembled fibers' tuning curves, and fibers with low spontaneous discharge rates tended to provide better resolution of stimulus components than fibers with high spontaneous rates. Strongly nonlinear behavior existed at higher stimulus intensities. In this, information was transmitted about progressively fewer signal components and about frequencies not present in the acoustic stimulus, and the component eliciting the largest response shifted away from the fiber's characteristic frequency and toward the edges of the stimulus spectrum. This high-intensity "edge enhancement" can result from the combined effects of a compressive input-output nonlinearity, suppression, and the fortuitous addition of internally generated combination tones. The data indicate that sufficient information exists for the auditory system to determine the frequencies of narrowly spaced stimulus components from the temporal fine structure of nerve fiber's responses.