Fuh-Cherng Jeng

Intracochlear and extracochlear ECAPs suggest antidromic action potentials.

With experimental animals, the electrically evoked compound action potential (ECAP) can be recorded from multiple sites (e.g., round window, intracranial and intracochlear sites). However, human ECAPs are typically recorded from intracochlear electrodes of the implanted array. To bridge this difference, we obtained ECAPs from cats using both intracochlear and nerve-trunk recording sites. We also sought to determine how recording the site influences the acquired evoked potential and how those differences may provide insight into basic excitation properties. In the main experiment, ECAPs were recorded from four acutely deafened cats after implanting a Nucleus-style banded electrode array. Potentials were recorded from an electrode positioned on the nerve trunk and an intracochlear electrode. We manipulated stimulus level, electrode configuration (monopolar vs bipolar) and stimulus polarity, variables that influence the site of excitation. Intracochlear ECAPs were found to be an order of magnitude greater than those obtained with the nerve-trunk electrode. Also, compared with the nerve-trunk potentials, the intracochlear ECAPs more closely resembled those obtained from humans in that latencies were shorter and the waveform morphology was typically biphasic (a negative peak followed by a positive peak). With anodic monophasic stimuli, the ECAP had a unique positive-to-negative morphology which we attributed to antidromic action potentials resulting from a relatively central site of excitation. We also collected intracochlear ECAPs from twenty Nucleus 24 implant users. Compared with the feline ECAPs, the human potentials had smaller amplitudes and longer latencies. It is not clear what underlies these differences, although several factors are considered.

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 response to intracochlear electric stimuli following furosemide treatment

The influence of functional hair cells on electrical stimulation of the auditory nerve is an important issue as individuals with significant residual hearing are now cochlear implant candidates. Previous work has shown that chemical deafening during the course of acute experiments changes the auditory nerves responses to electrical stimulation [Third Quarterly Progress Report, NIH contract N01-DC-9-2106 (2000), Final Report, NIH Contract N01-DC-9-2106 (2002)]. This study extended that work by investigating the changes and subsequent recovery following furosemide injections which reversibly impair hair-cell function [Hear. Res. (1980) 79-89; Hear. Res. 14 (1984) 305-314, J. Physiol. 347 (1984) 685-696; Hear. Res. 71 (1993) 202-207]. Acoustic sensitivity of guinea pig subjects was repeatedly monitored with the click-evoked compound action potential. Responses to single biphasic electric pulses and biphasic electric pulse trains delivered by a monopolar intracochlear electrode were also repeatedly assessed using the electrically evoked compound action potential (ECAP). Our measures demonstrated a clear relationship between the state of hair-cell function and ECAP responses, as changes in the latter coincided with the loss or recovery of acoustic sensitivity. ECAP growth functions demonstrated increased slope and increased maximum (saturation) amplitude. Both trends were reversible and followed approximately the time course of post-furosemide hearing recovery. Additional changes were observed using electric pulse-train stimulation: (1) the magnitude of ECAP amplitude alternation (observed in response to successive stimulus pulses) increased, (2) the degree of ECAP adaptation (measured 80-100 ms after pulse-train onset) increased, and (3) the degree of refractoriness (measured by the ratio of ECAP amplitudes to the second and first pulses) tended to increase. All these trends are consistent with the hypothesis that functional hair cells desynchronize the population of auditory nerve fibers, thereby changing the electrically evoked responses. Viable hair cells may therefore provide positive effects on auditory response to electric stimuli delivered to implant patients with residual hearing, as they may enhance the random activity of the stimulated nerve.

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.

Effects of acoustic noise on the auditory nerve compound action potentials evoked by electric pulse trains

This study investigated the effects of acoustic noise on the auditory nerve compound action potentials in response to electric pulse trains. Subjects were adult guinea pigs, implanted with a minimally invasive electrode to preserve acoustic sensitivity. Electrically evoked compound action potentials (ECAP) were recorded from the auditory nerve trunk in response to electric pulse trains both during and after the presentation of acoustic white noise. Simultaneously presented acoustic noise produced a decrease in ECAP amplitude. The effect of the acoustic masker on the electric probe was greatest at the onset of the acoustic stimulus and it was followed by a partial recovery of the ECAP amplitude. Following cessation of the acoustic noise, ECAP amplitude recovered over a period of approximately 100-200 ms. The effects of the acoustic noise were more prominent at lower electric pulse rates (interpulse intervals of 3 ms and higher). At higher pulse rates, the ECAP adaptation to the electric pulse train alone was larger and the acoustic noise, when presented, produced little additional effect. The observed effects of noise on ECAP were the greatest at high electric stimulus levels and, for a particular electric stimulus level, at high acoustic noise levels.

Acoustic-electric interactions in the guinea pig auditory nerve: simultaneous and forward masking of the electrically evoked compound action potential.

The study investigated the time course of the effects of acoustic and electric stimulation on the electrically evoked compound action potential (ECAP). Adult guinea pigs were used in acute experimental sessions. Bursts of acoustic noise and high-rate (5000 pulses/s) electric pulse trains were used as maskers. Biphasic electric pulses were used as probes. ECAPs were recorded from the auditory nerve trunk. Simultaneous masking of the ECAP with acoustic noise featured an onset effect and a decrease in the amount of masking to a steady state. It was characterized by a two-component exponential function. The amount of masking increased with masker level and decreased with probe level. Post-stimulatory ECAP recovery often featured a non-monotonic time course, described by a three-component exponent. Electric maskers produced similar post-stimulatory effects in hearing and acutely deafened subjects. Acoustic stimulation affects the ECAP in a level- and time-dependent manner. Simultaneous masking follows a time course comparable to that of adaptation to an acoustic stimulus. Refractoriness, spontaneous activity, and adaptation are suggested to play a role in ECAP recovery. Post-stimulatory changes in synchrony, possibly due to recovery of spontaneous activity and an additional hair-cell independent mechanism, are hypothesized to contribute to the observed non-monotonicity of recovery.

Electrically Evoked Auditory Steady-State Responses in Guinea Pigs

Most cochlear implant systems available today provide the user with information about the envelope of the speech signal. The goal of this study was to explore the feasibility of recording electrically evoked auditory steady-state response (ESSR) and in particular to evaluate the degree to which the response recorded using electrical stimulation could be separated from stimulus artifact. Sinusoidally amplitude-modulated electrical stimuli with alternating polarities were used to elicit the response in adult guinea pigs. Separation of the stimulus artifact from evoked neural responses was achieved by summing alternating polarity responses or by using spectral analysis techniques. The recorded response exhibited physiological response properties including a pattern of nonlinear growth and their abolishment following euthanasia or administration of tetrodotoxin. These findings demonstrate that the ESSR is a response generated by the auditory system and can be separated from electrical stimulus artifact. As it is evoked by a stimulus that shares important features of cochlear implant stimulation, this evoked potential may be useful in either clinical or basic research efforts.

Electrically Evoked Auditory Steady-State Responses in a Guinea Pig Model: Latency Estimates and Effects of Stimulus Parameters

Cochlear implant speech processors typically extract envelope information of speech signals for presentation to the auditory nerve as modulated trains of electric pulses. Recent studies showed the feasibility of recording, at the scalp, the electrically evoked auditory steady-state response using amplitude-modulated electric stimuli. Sinusoidally amplitude-modulated electric stimuli were used to elicit such responses from guinea pigs in order to characterize this response. Response latencies were derived to provide insight regarding neural generator sites. Two distinct sites, one cortical and another more peripheral, were indicated by latency estimates of 22 and 2 ms, respectively, with the former evoked by lower (13–49 Hz) and the latter by higher (55–320 Hz) modulation frequencies. Furthermore, response amplitudes declined with increasing carrier frequency, exhibited a compressive growth with increasing modulation depths, and were sensitive to modulation depths to as low as 5%.

Binaural interactions of electrically and acoustically evoked responses recorded from the inferior colliculus of guinea pigs

Binaural interactions within the inferior colliculus (IC) elicited by electric and acoustic stimuli were investigated in this study. Using a guinea pig model, binaural acoustic stimuli were presented with different time delays, as were combinations of binaural electric and acoustic stimuli. Averaged evoked potentials were measured using electrodes inserted into the central nucleus of the IC to obtain the binaural interaction component (BIC), computed by subtracting the sum of the two monaural responses from the binaural response. The BICs to acoustic-acoustic stimulation and electric-acoustic stimulation were found to be similar. The BIC amplitude increased with stimulus intensity, but the shapes of the delay functions were similar across the levels tested. The gross-potential data are thus consistent with the thesis that the central auditory system processes binaural electric and acoustic stimuli in a similar manner. These results suggest that the binaural auditory system can process combinations of electric and acoustic stimulation presented across ears and that evoked gross potentials may be used to measure such interaction.

Effects of temporal properties on compound action potentials in response to amplitude-modulated electric pulse trains in guinea pigs.

The electrically evoked compound action potential (ECAP) of the auditory nerve in response to amplitude-modulated pulse trains varies over time, but the response amplitudes are not linearly proportional to the level of stimulus pulses. At least two mechanisms could contribute to the deviations of the ECAP response pattern from that of the stimulus envelope. The first mechanism is time-invariant or stationary that reflects the non-linear growth of response amplitude with changes in stimulus level that is evident in the response to single pulses. This can be considered a time-invariant or stationary effect. The second mechanism is time-variant or non-stationary and reflects neural refractoriness and adaptation. The purpose of this study was to characterize the auditory nerve responses to amplitude-modulated pulse trains and also to evaluate the extent to which the stationary and non-stationary effects may contribute to those responses. ECAP amplitudes were predicted from single-pulse growth functions of the auditory nerve to account for time-invariant effects. Linear regression was performed on the measured vs. predicted ECAP amplitudes to quantify the discrepancies between the two datasets, thereby separating the influence of non-linear growth from time-varying effects on ECAP amplitudes. The results demonstrated a bandpass function of the modulated response amplitudes, with a low-cutoff modulation frequency at 300Hz and a high-cutoff modulation frequency at 800Hz, depending on the carrier pulse rate. The relative contribution of the temporal effects on ECAP amplitudes is greatest at low stimulus levels and low modulation depths.