Changes Across Time in Spike Rate and Spike Amplitude of Auditory Nerve Fibers Stimulated by Electric Pulse Trains

We undertook a systematic evaluation of spike rates and spike amplitudes of auditory nerve fiber (ANF) responses to trains of electric current pulses. Measures were obtained from acutely deafened cats to examine time-related changes free from the effects of hair-cell and synaptic adaptation. Such data relate to adaptation that likely occurs in ANFs of cochlear-implant users. A major goal was to determine and compare rate adaptation observed at different pulse rates (primarily 250, 1000, and 5000 pulse/s) and describe them using decaying exponential models similar to those used in acoustic studies. Rate-vs.-time functions were best described by two-exponent models and produced time constants similar to (although slightly greater than) the “rapid” and “short-term” components described in acoustic studies. There was little dependence of these time constants on onset spike rate, but pulse-rate effects were noted. Spike amplitude changes followed a time course different from that of rate adaptation consistent with a process related to ANF interspike intervals. The fact that two time constants governed rate adaptation in electrically stimulated and deafened fibers suggests that future computational models of adaptation should not only include hair cell and synapse components, but also components determined by fiber membrane characteristics.     

Electrical Excitation of the Acoustically Sensitive Auditory Nerve: Single-Fiber Responses to Electric Pulse Trains

Nearly all studies on auditory-nerve responses to electric stimuli have been conducted using chemically deafened animals so as to more realistically model the implanted human ear that has typically been profoundly deaf. However, clinical criteria for implantation have recently been relaxed. Ears with “residual” acoustic sensitivity are now being implanted, calling for the systematic evaluation of auditory-nerve responses to electric stimuli as well as combined electric and acoustic stimuli in acoustically sensitive ears. This article presents a systematic investigation of single-fiber responses to electric stimuli in acoustically sensitive ears. Responses to 250 pulse/s electric pulse trains were collected from 18 cats. Properties such as threshold, dynamic range, and jitter were found to differ from those of deaf ears. Other types of fiber activity observed in acoustically sensitive ears (i.e., spontaneous activity and electrophonic responses) were found to alter the temporal coding of electric stimuli. The electrophonic response, which was shown to greatly change the information encoded by spike intervals, also exhibited fast adaptation relative to that observed in the “direct” response to electric stimuli. More complex responses, such as “buildup” (increased responsiveness to successive pulses) and “bursting” (alternating periods of responsiveness and unresponsiveness) were observed. Our findings suggest that bursting is a response unique to sustained electric stimulation in ears with functional hair cells.     

Auditory Nerve Fiber Responses to Combined Acoustic and Electric Stimulation

Persons with a prosthesis implanted in a cochlea with residual acoustic sensitivity can, in some cases, achieve better speech perception with “hybrid” stimulation than with either acoustic or electric stimulation presented alone. Such improvements may involve “across auditory-nerve fiber” processes within central nuclei of the auditory system and within-fiber interactions at the level of the auditory nerve. Our study explored acoustic–electric interactions within feline auditory nerve fibers (ANFs) so as to address two goals. First, we sought to better understand recent results that showed non-monotonic recovery of the electrically evoked compound action potential (ECAP) following acoustic masking (Nourski et al. 2007, Hear. Res. 232:87–103). We hypothesized that post-masking changes in ANF temporal properties and responsiveness (spike rate) accounted for the ECAP results. We also sought to describe, more broadly, the changes in ANF responses that result from prior acoustic stimulation. Five response properties—spike rate, latency, jitter, spike amplitude, and spontaneous activity—were examined. Post-masking reductions in spike rate, within-fiber jitter and across-fiber variance in latency were found, with the changes in temporal response properties limited to ANFs with high spontaneous rates. Thus, our results suggest how non-monotonic ECAP recovery occurs for ears with spontaneous activity, but cannot account for that pattern of recovery when there is no spontaneous activity, including the results from the presumably deafened ears used in the Nourski et al. (2007) study. Finally, during simultaneous (electric+acoustic) stimulation, the degree of electrically driven spike activity had a strong influence on spike rate, but did not affect spike jitter, which apparently was determined by the acoustic noise stimulus or spontaneous activity.     

Changes in Auditory Nerve Responses Across the Duration of Sinusoidally Amplitude-Modulated Electric Pulse-Train Stimuli

Response rates of auditory nerve fibers (ANFs) to electric pulse trains change over time, reflecting substantial spike-rate adaptation that depends on stimulus parameters. We hypothesize that adaptation affects the representation of amplitude-modulated pulse trains used by cochlear prostheses to transmit speech information to the auditory system. We recorded cat ANF responses to sinusoidally amplitude-modulated (SAM) trains with 5,000 pulse/s carriers. Stimuli delivered by a monopolar intracochlear electrode had fixed modulation frequency (100 Hz) and depth (10%). ANF responses were assessed by spike-rate measures, while representation of modulation was evaluated by vector strength (VS) and the fundamental component of the fast Fourier transform (F₀ amplitude). These measures were assessed across the 400 ms duration of pulse-train stimuli, a duration relevant to speech stimuli. Different stimulus levels were explored and responses were categorized into four spike-rate groups to assess level effects across ANFs. The temporal pattern of rate adaptation to modulated trains was similar to that of unmodulated trains, but with less rate adaptation. VS to the modulator increased over time and tended to saturate at lower spike rates, while F₀ amplitude typically decreased over time for low driven rates and increased for higher driven rates. VS at moderate and high spike rates and degree of F₀ amplitude temporal changes at low and moderate spike rates were positively correlated with the degree of rate adaptation. Thus, high-rate carriers will modify the ANF representation of the modulator over time. As the VS and F₀ measures were sensitive to adaptation-related changes over different spike-rate ranges, there is value in assessing both measures.     

Neural Masking by Sub-threshold Electric Stimuli: Animal and Computer Model Results

Electric stimuli can prosthetically excite auditory nerve fibers to partially restore sensory function to individuals impaired by profound or severe hearing loss. While basic response properties of electrically stimulated auditory nerve fibers (ANF) are known, responses to complex, time-changing stimuli used clinically are inadequately understood. We report that forward-masker pulse trains can enhance and reduce ANF responsiveness to subsequent stimuli and the novel observation that sub-threshold (nonspike-evoking) electric trains can reduce responsiveness to subsequent pulse-train stimuli. The effect is observed in the responses of cat ANFs and shown by a computational biophysical ANF model that simulates rate adaptation through integration of external potassium cation (K) channels. Both low-threshold (i.e., Klt) and high-threshold (Kht) channels were simulated at each node of Ranvier. Model versions without Klt channels did not produce the sub-threshold effect. These results suggest that some such accumulation mechanism, along with Klt channels, may underlie sub-threshold masking observed in cat ANF responses. As multichannel auditory prostheses typically present sub-threshold stimuli to various ANF subsets, there is clear relevance of these findings to clinical situations.     

The Dependence of Auditory Nerve Rate Adaptation on Electric Stimulus Parameters, Electrode Position, and Fiber Diameter: A Computer Model Study

This paper describes results from a stochastic computational neuron model that simulates the effects of rate adaptation on the responses to electrical stimulation in the form of pulse trains. We recently reported results from a single-node computational model that included a novel element that tracks external potassium ion concentration so as to modify membrane voltage and cause adaptation-like responses. Here, we report on an improved version of the model that incorporates the anatomical components of a complete feline auditory nerve fiber (ANF) so that conduction velocity and effects of manipulating the site of excitation can be evaluated. Model results demonstrate rate adaptation and changes in spike amplitude similar to those reported for feline ANFs. Changing the site of excitation from a central to a peripheral axonal site resulted in plausible changes in latency and relative spread (i.e., dynamic range). Also, increasing the distance between a modeled ANF and a stimulus electrode tended to decrease the degree of rate adaptation observed in pulse-train responses. This effect was clearly observed for high-rate (5,000 pulse/s) trains but not low-rate (250 pulse/s) trains. Finally, for relatively short electrode-to-ANF distances, increases in modeled ANF diameter increased the degree of rate adaptation. These results are compared against available feline ANF data, and possible effects of individual parameters are discussed.     

Higher Sensitivity of Human Auditory Nerve Fibers to Positive Electrical Currents

Most contemporary cochlear implants (CIs) stimulate the auditory nerve with trains of amplitude-modulated, symmetric biphasic pulses. Although both polarities of a pulse can depolarize the nerve fibers and generate action potentials, it remains unknown which of the two (positive or negative) phases has the stronger effect. Understanding the effects of pulse polarity will help to optimize the stimulation protocols and to deliver the most relevant information to the implant listeners. Animal experiments have shown that cathodic (negative) current flows are more effective than anodic (positive) ones in eliciting neural responses, and this finding has motivated the development of novel speech-processing algorithms. In this study, we show electrophysiologically and psychophysically that the human auditory system exhibits the opposite pattern, being more sensitive to anodic stimulation. We measured electrically evoked compound action potentials in CI listeners for phase-separated pulses, allowing us to tease out the responses to each of the two opposite-polarity phases. At an equal stimulus level, the anodic phase yielded the larger response. Furthermore, a measure of psychophysical masking patterns revealed that this polarity difference was still present at higher levels of the auditory system and was therefore not solely due to antidromic propagation of the neural response. This finding may relate to a particular orientation of the nerve fibers relative to the electrode or to a substantial degeneration and demyelination of the peripheral processes. Potential applications to improve CI speech-processing strategies are discussed.     

Effects of Pulse Phase Duration and Location of Stimulation Within the Inferior Colliculus on Auditory Cortical Evoked Potentials in a Guinea Pig Model

The auditory midbrain implant (AMI), which consists of a single shank array designed for stimulation within the central nucleus of the inferior colliculus (ICC), has been developed for deaf patients who cannot benefit from a cochlear implant. Currently, performance levels in clinical trials for the AMI are far from those achieved by the cochlear implant and vary dramatically across patients, in part due to stimulation location effects. As an initial step towards improving the AMI, we investigated how stimulation of different regions along the isofrequency domain of the ICC as well as varying pulse phase durations and levels affected auditory cortical activity in anesthetized guinea pigs. This study was motivated by the need to determine in which region to implant the single shank array within a three-dimensional ICC structure and what stimulus parameters to use in patients. Our findings indicate that complex and unfavorable cortical activation properties are elicited by stimulation of caudal–dorsal ICC regions with the AMI array. Our results also confirm the existence of different functional regions along the isofrequency domain of the ICC (i.e., a caudal–dorsal and a rostral–ventral region), which has been traditionally unclassified. Based on our study as well as previous animal and human AMI findings, we may need to deliver more complex stimuli than currently used in the AMI patients to effectively activate the caudal ICC or ensure that the single shank AMI is only implanted into a rostral–ventral ICC region in future patients.     

A Dual-Process Integrator–Resonator Model of the Electrically Stimulated Human Auditory Nerve

A phenomenological dual-process model of the electrically stimulated human auditory nerve is presented and compared to threshold and loudness data from cochlear implant users. The auditory nerve is modeled as two parallel processes derived from linearized equations of conductance-based models. The first process is an integrator, which dominates stimulation for short-phase duration biphasic pulses and high-frequency sinusoidal stimuli. It has a relatively short time constant (0.094 ms) arising from the passive properties of the membrane. The second process is a resonator, which induces nonmonotonic functions of threshold vs frequency with minima around 80 Hz. The ion channel responsible for this trend has a relatively large relaxation time constant of about 1 ms. Membrane noise is modeled as a Gaussian noise, and loudness sensation is assumed to relate to the probability of firing of a neuron during a 20-ms rectangular window. Experimental psychophysical results obtained in seven previously published studies can be interpreted with this model. The model also provides a physiologically based account of the nonmonotonic threshold vs frequency functions observed in biphasic and sinusoidal stimulation, the large threshold decrease obtained with biphasic pulses having a relatively long inter-phase gap and the effects of asymmetric pulses.     

Dynamical Instability Determines the Effect of Ongoing Noise on Neural Firing

At low stimulation rates, electrically stimulated auditory nerve fibers typically fire regularly, in lock-step to the applied stimulus. At high stimulation rates, however, these same fibers fire irregularly. Firing irregularity has been attributed to the random opening and closing of voltage-gated sodium channels at the spike generation site. We demonstrate, however, that the nonlinear dynamics of neural excitation and refractoriness embodied in the FitzHugh–Nagumo (FN) model produce realistic firing irregularity at high stimulus rates, even in the complete absence of ongoing physiological noise. Indeed, we show that ongoing noise can actually regularize the response at low discharge rates. The degree of stimulus-dependent irregularity is determined not so much by the level of ongoing physiological noise as by the dynamical instability. Our work suggests that the dynamical instability, quantified by the Lyapunov exponent, controls neural sensitivity to input signals and to physiological noise, as well the amount of mutual desynchronization between similarly stimulated fibers. This instability, quantified by the value of the Lyapunov exponent, may play a critical role in determining modulation sensitivity and dynamic range in cochlear implants. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Effects of Electrical Stimulation of Olivocochlear Fibers in Cochlear Potentials in the Chinchilla

The mammalian cochlea has two types of sensory cells; inner hair cells, which receive auditory-nerve afferent innervation, and outer hair cells, innervated by efferent axons of the medial olivocochlear (MOC) system. The role of the MOC system in hearing is still controversial. Recently, by recording cochlear potentials in behaving chinchillas, we suggested that one of the possible functions of the efferent system is to reduce cochlear sensitivity during attention to other sensory modalities (Delano et al. in J Neurosci 27:4146–4153, 2007). However, in spite of these compelling results, the physiological effects of electrical MOC activation on cochlear potentials have not been described in detail in chinchillas. The main objective of the present work was to describe these efferent effects in the chinchilla, comparing them with those in other species and in behavioral experiments. We activated the MOC efferent axons in chinchillas with sectioned middle-ear muscles by applying current pulses at the fourth-ventricle floor. Auditory-nerve compound action potentials (CAP) and cochlear microphonics (CM) were acquired in response to clicks and tones of several frequencies, using a round-window electrode. Electrical efferent stimulation produced CAP amplitude suppressions reaching up to 11 dB. They were higher for low to moderate sound levels. Additionally, CM amplitude increments were found, the largest (≤ 2.5 dB) for low intensity tones. CAP suppression was present at all stimulus frequencies, but was greatest for 2 kHz. CM increments were highest for low-frequency tones, and almost absent at high frequencies. We conclude that the effect obtained in chinchilla is similar to but smaller than that observed in cats, and that the effects seen in awake chinchillas, albeit different in magnitude, are consistent with the activation of efferent fibers.     

Topography of Auditory Nerve Projections to the Cochlear Nucleus in Cats after Neonatal Deafness and Electrical Stimulation by a Cochlear Implant

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

Modulation Enhancement in the Electrical Signal Improves Perception of Interaural Time Differences with Bimodal Stimulation

Interaural timing cues are important for sound source localization and for binaural unmasking of speech that is spatially separated from interfering sounds. Users of a cochlear implant (CI) with residual hearing in the non-implanted ear (bimodal listeners) can only make very limited use of interaural timing cues with their clinical devices. Previous studies showed that bimodal listeners can be sensitive to interaural time differences (ITDs) for simple single- and three-channel stimuli. The modulation enhancement strategy (MEnS) was developed to improve the ITD perception of bimodal listeners. It enhances temporal modulations on all stimulated electrodes, synchronously with modulations in the acoustic signal presented to the non-implanted ear, based on measurement of the amplitude peaks occurring at the rate of the fundamental frequency in voiced phonemes. In the first experiment, ITD detection thresholds were measured using the method of constant stimuli for five bimodal listeners for an artificial vowel, processed with either the advanced combination encoder (ACE) strategy or with MEnS. With MEnS, detection thresholds were significantly lower, and for four subjects well within the physically relevant range. In the second experiment, the extent of lateralization was measured in three subjects with both strategies, and ITD sensitivity was determined using an adaptive procedure. All subjects could lateralize sounds based on ITD and sensitivity was significantly better with MEnS than with ACE. The current results indicate that ITD cues can be provided to bimodal listeners with modified sound processing.