High-rate Electrical Stimulation Research Articles

Short and long-term adaptation in the auditory nerve stimulated with high-rate electrical pulse trains are better described by a power law

Despite the introduction of many new sound-coding strategies speech perception outcomes in cochlear implant listeners have leveled off. Computer models may help speed up the evaluation of new sound-coding strategies, but most existing models of auditory nerve responses to electrical stimulation include limited temporal detail, as the effects of longer stimulation, such as adaptation, are not well-studied. Measured neural responses to stimulation with both short (400 ms) and long (10 min) duration high-rate (5kpps) pulse trains were compared in terms of spike rate and vector strength (VS) with model outcomes obtained with different forms of adaptation. A previously published model combining biophysical and phenomenological approaches was adjusted with adaptation modeled as a single decaying exponent, multiple exponents and a power law. For long duration data, power law adaptation by far outperforms the single exponent model, especially when it is optimized per fiber. For short duration data, all tested models performed comparably well, with slightly better performance of the single exponent model for VS and of the power law model for the spike rates. The power law parameter sets obtained when fitted to the long duration data also yielded adequate predictions for short duration stimulation, and vice versa. The power law function can be approximated with multiple exponents, which is physiologically more viable. The number of required exponents depends on the duration of simulation; the 400 ms data was well-replicated by two exponents (23 and 212 ms), whereas the 10-minute data required at least seven exponents (ranging from 4 ms to 600 s). Adaptation of the auditory nerve to high-rate electrical stimulation can best be described by a power-law or a sum of exponents. This gives an adequate fit for both short and long duration stimuli, such as CI speech segments.

Electrical stimulation of sympathetic neurons induces autocrine/paracrine effects of NGF mediated by TrkA

Neuronal remodeling with increased sympathetic innervation density has been implicated in the pathogenesis of atrial fibrillation (AF). Recently, increased transcardiac nerve growth factor (NGF) levels were observed in a canine model of AF. Whether atrial myocytes or cardiac sympathetic neurons are the source of neurotrophins, and whether NGF is the main neurotrophic factor contributing to sympathetic nerve sprouting (SNS) in AF still remains unclear. Therefore, neonatal rat atrial myocytes were cultured under conditions of high frequency electrical field stimulation (HFES) to mimic rapid atrial depolarization. Likewise, sympathetic neurons from the superior cervical ganglia of neonatal rats were exposed to HFES to simulate the physiological effect of sympathetic stimulation. Real-time PCR, ELISA and Western blots were performed to analyze the expression pattern of NGF and neurotrophin-3 (NT-3). Baseline NGF and NT-3 content was 3-fold higher in sympathetic neurons than in atrial myocytes (relative NGF protein expression: 1±0.0 vs. 0.37±0.11, all n=5, p<0.05). HFES of sympathetic neurons induced a frequency dependent NGF and NT-3 gene and protein up-regulation (relative NGF protein expression: 0Hz=1±0.0 vs. 5Hz=1.13±0.19 vs. 50Hz=1.77±0.08, all n=5, 0Hz/5Hz vs. 50Hz p<0.05), with a subsequent increase of growth associated protein 43 (GAP-43) expression and morphological SNS. Moreover, HFES of sympathetic neurons increased the tyrosine kinase A (TrkA) receptor expression. HFES induced neurotrophic effects could be abolished by lidocaine, TrkA blockade or NGF neutralizing antibodies, while NT-3 neutralizing antibodies had no significant effect on SNS. In neonatal rat atrial myocytes, HFES resulted in myocyte hypertrophy accompanied by an increase in NT-3 and a decrease in NGF expression. In summary, this study provides evidence that high-rate electrical stimulation of sympathetic neurons mediates nerve sprouting by an increase in NGF expression that targets the TrkA receptor in an autocrine/paracrine manner.

A novel stimulus artifact removal technique for high-rate electrical stimulation

Electrical stimulus artifact corrupting electrophysiological recordings often makes the subsequent analysis of the underlying neural response difficult. This is particularly evident when investigating short-latency neural activity in response to high-rate electrical stimulation. We developed and evaluated an off-line technique for the removal of stimulus artifact from electrophysiological recordings. Pulsatile electrical stimulation was presented at rates of up to 5000 pulses/s during extracellular recordings of guinea pig auditory nerve fibers. Stimulus artifact was removed by replacing the sample points at each stimulus artifact event with values interpolated along a straight line, computed from neighbouring sample points. This technique required only that artifact events be identifiable and that the artifact duration remained less than both the inter-stimulus interval and the time course of the action potential. We have demonstrated that this computationally efficient sample-and-interpolate technique removes the stimulus artifact with minimal distortion of the action potential waveform. We suggest that this technique may have potential applications in a range of electrophysiological recording systems.

An Electric Frequency-to-place Map for a Cochlear Implant Patient with Hearing in the Nonimplanted Ear

The aim of this study was to relate the pitch of high-rate electrical stimulation delivered to individual cochlear implant electrodes to electrode insertion depth and insertion angle. The patient (CH1) was able to provide pitch matches between electric and acoustic stimulation because he had auditory thresholds in his nonimplanted ear ranging between 30 and 60 dB HL over the range, 250 Hz to 8 kHz. Electrode depth and insertion angle were measured from high-resolution computed tomography (CT) scans of the patient's temporal bones. The scans were used to create a 3D image volume reconstruction of the cochlea, which allowed visualization of electrode position within the scala. The method of limits was used to establish pitch matches between acoustic pure tones and electric stimulation (a 1,652-pps, unmodulated, pulse train). The pitch matching data demonstrated that, for insertion angles of greater than 450 degrees or greater than approximately 20 mm insertion depth, pitch saturated at approximately 420 Hz. From 20 to 15 mm insertion depth pitch estimates were about one-half octave lower than the Greenwood function. From 13 to 3 mm insertion depth the pitch estimates were approximately one octave lower than the Greenwood function. The pitch match for an electrode only 3.4 mm into the cochlea was 3,447 Hz. These data are consistent with other reports, e.g., Boëx et al. (2006), of a frequency-to-place map for the electrically stimulated cochlea in which perceived pitches for stimulation on individual electrodes are significantly lower than those predicted by the Greenwood function for stimulation at the level of the hair cell.

Changes in pitch with a cochlear implant over time.

In the normal auditory system, the perceived pitch of a tone is closely linked to the cochlear place of vibration. It has generally been assumed that high-rate electrical stimulation by a cochlear implant electrode also evokes a pitch sensation corresponding to the electrode's cochlear place ("place" code) and stimulation rate ("temporal" code). However, other factors may affect electric pitch sensation, such as a substantial loss of nearby nerve fibers or even higher-level perceptual changes due to experience. The goals of this study were to measure electric pitch sensations in hybrid (short-electrode) cochlear implant patients and to examine which factors might contribute to the perceived pitch. To look at effects of experience, electric pitch sensations were compared with acoustic tone references presented to the non-implanted ear at various stages of implant use, ranging from hookup to 5 years. Here, we show that electric pitch perception often shifts in frequency, sometimes by as much as two octaves, during the first few years of implant use. Additional pitch measurements in more recently implanted patients at shorter time intervals up to 1 year of implant use suggest two likely contributions to these observed pitch shifts: intersession variability (up to one octave) and slow, systematic changes over time. We also found that the early pitch sensations for a constant electrode location can vary greatly across subjects and that these variations are strongly correlated with speech reception performance. Specifically, patients with an early low-pitch sensation tend to perform poorly with the implant compared to those with an early high-pitch sensation, which may be linked to less nerve survival in the basal end of the cochlea in the low-pitch patients. In contrast, late pitch sensations show no correlation with speech perception. These results together suggest that early pitch sensations may more closely reflect peripheral innervation patterns, while later pitch sensations may reflect higher-level, experience-dependent changes. These pitch shifts over time not only raise questions for strict place-based theories of pitch perception, but also imply that experience may have a greater influence on cochlear implant perception than previously thought.

Rate limitation and onset dominance in the discrimination of high-frequency click trains with dynamic envelope ITDs

Several studies have shown that binaural processing at high carrier frequency is limited to relatively slow modulations, suggesting profound consequences for binaural processing of high-rate electrical stimulation by cochlear implants (CIs). In this study, we measured normal-hearing-envelope ITD thresholds for Gaussian impulses (clicks) with 4000 Hz carrier frequency and 2 ms total duration (BW approximately 900 Hz) and for 16-click trains with rates of 100, 200, or 500 pps. For click trains, right-leading ITDs were static (condition RR), increased linearly from diotic (condition 0R), or decreased linearly toward diotic (condition R0). Thresholds were calculated from the largest ITD in each stimulus (i.e., the onset of R0 or offset of 0R trains). Consistent with previous results for normal hearing and bilaterally implanted subjects, thresholds were strongly dependent on ICI. Low-rate (100 pps) thresholds improved for 16-click trains relative to single clicks in all conditions, while high-rate (500 pps) thresholds were similar to single clicks for RR and R0 stimuli. In condition 0R, 500 pps ITD thresholds were elevated and comparable to monaural rate discrimination. The results suggest an inability to lateralize high-rate stimuli in the absence of onset ITDs and have important consequences for binaural information processing with cochlear implants.

An integrate-and-fire-based auditory nerve model and its response to high-rate pulse train

In this paper, a simple but efficient integrate-and-fire-based auditory nerve (AN) model is introduced. The model uses a Gaussian noise and a refractory function to describe the stochastic membrane potential fluctuation and the refractory effect during the neural firing, respectively. The proposed model is characterized by its computation ease and efficiency. Results of the model-based simulation showed that the neural firing produced an enhanced temporal representation of the stimulus waveform at the high-rate electrical stimulation. It was also found that there was an optimal pulse width to represent the temporal structure of the stimulus waveform. The proposed model would facilitate the further investigation of AN's response to different input stimulations, and help us to develop novel electrical stimulation strategies for cochlear implants in the future.

Effects of high-rate electrical stimulation upon firing in modelled and real neurons.

Many medical devices use high-rate, low-amplitude currents to affect neural function. This study examined the effect of stimulation rate upon action potential threshold and sustained firing rate for two model neurons, the rabbit myelinated fibre and the unmyelinated leech touch sensory cell. These model neurons were constructed with the NEURON simulator from electrophysiological data. Alternating-phase current pulses (0-1250 Hz), of fixed phase duration (0.2 ms), were used to stimulate the neurons, and propagation success or failure was measured. One effect of the high pulse rates was to cause a net depolarisation, and this was verified by the relief of action potential conduction block by 500 Hz extracellular stimulation in leech neurons. The models also predicted that the neurons would maintain maximum sustained firing at a number of different stimulation rates. For example, at twice threshold, the myelinated model followed the stimulus up to 500 Hz stimulation, half the stimulus rate up to 850 Hz stimulation, and it did not fire at 1250 Hz stimulation. By contrast, the unmyelinated neuron model had a lower maximum firing rate of 190 Hz, and this rate was obtained at a number of stimulation rates, up to 1250 Hz. The myelinated model also predicted sustained firing with 1240 Hz stimulation at threshold current, but no firing when the current level was doubled. Most of these effects are explained by the interaction of stimulus pulses with the cell's refractory period.

Role of field intensity in the biological effectiveness of millimeter waves at a resonance frequency

The study replicated the effect of low-intensity millimeter waves (MMW) on isolated nerve function and characterized its dependence on radiation intensity. MMW exposures lasted for 23 min at 0.02, 0.1, 0.5, or 2.6 mW cm −2 (41.34 GHz) and were accompanied by a high-rate electrical stimulation of the nerve (HRS, 20 twin pulses s −1, 9 ms interpulse interval). MMW had no effect on the conditioning compound action potentials (CAPs), but significantly attenuated the HRS-caused decrease of the test CAPs. The magnitude of this effect was virtually the same (20–25%) at field intensities of 0.02, 0.1, and 2.6 mW cm −2. Irradiation at 0.5 mW cm −2m however, did not produce statistically significant changes. The results are consistent with our earlier observations of this MMW effect and provide further evidence for its nonthermal mechanism.

Chronic electrical stimulation of the auditory nerve at high stimulus rates: a physiological and histopathological study

A major factor associated with recent improvements in the clinical performance of cochlear implant patients has been the development of speech-processing strategies based on high stimulation rates. While these processing strategies show clear clinical advantage, we know little of their long-term safety implications. The present study was designed to evaluate the physiological and histopathological effects of long-term intracochlear electrical stimulation using these high rates. Thirteen normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods of up to 2100 h using either two pairs of bipolar or three monopolar stimulating electrodes. Stimuli consisted of short duration (25–50 μs/phase) charge-balanced biphasic current pulses presented at 1000 pulses per second (pps) per channel for monopolar stimulation, and 2000 pps/channel for bipolar stimulation. The electrodes were shorted between current pulses to minimize any residual direct current, and the pulse trains were presented using a 50% duty cycle (500 ms on; 500 ms off) in order to simulate speech. Both acoustic (ABR) and electrical (EABR) auditory brainstem responses were recorded periodically during the chronic stimulation program. All cochleas showed an increase in the click-evoked ABR threshold following implant surgery; however, recovery to near-normal levels occurred in approximately half of the stimulated cochleas 1 month post-operatively. The use of frequency-specific stimuli indicated that the most extensive hearing loss generally occurred in the high-frequency basal region of the cochlea (12 and 24 kHz) adjacent to the stimulating electrode. However, thresholds at lower frequencies (2, 4 and 8 kHz), appeared at near-normal levels despite long-term electrode implantation and electrical stimulation. Our longitudinal EABR results showed a statistically significant increase in threshold in nearly 40% of the chronically stimulated electrodes evaluated; however, the gradient of the EABR input/output (I/O) function (evoked potential response amplitude versus stimulus current) generally remained quite stable throughout the chronic stimulation period. Histopathological examination of the cochleas showed no statistically significant difference in ganglion cell densities between cochleas using monopolar and bipolar electrode configurations (P = 0.67), and no evidence of cochlear damage caused by high-rate electrical stimulation when compared with control cochleas. Indeed, there was no statistically significant relationship between spiral ganglion cell density and electrical stimulation (P = 0.459), or between the extent of loss of inner (IHC, P = 0.86) or outer (OHC, P = 0.30) hair cells and electrical stimulation. Spiral ganglion cell loss was, however, influenced by the degree of inflammation (P = 0.016) and electrode insertion trauma. These histopathological findings were consistent with the physiological data. Finally, electrode impedance, measured at completion of the chronic stimulation program, showed close correlation with the degree of tissue response adjacent to the electrode array. These results indicated that chronic intracochlear electrical stimulation, using carefully controlled charge-balanced biphasic current pulses at stimulus rates of up to 2000 pps/channel, does not appear to adversely affect residual auditory nerve elements or the cochlea in general. This study provides an important basis for the safe application of improved speech-processing strategies based on high-rate electrical stimulation.

Effects of chronic high-rate electrical stimulation on the cochlea and eighth nerve in the deafened guinea pig

This study was undertaken to examine the effects of chronic high-rate stimulation on the eighth nerve and cochlea. Fifty-four male pigmented guinea pigs were deafened and implanted with single ball electrodes in scala tympani. Four groups of animals received chronic electrical stimulation at a level of 5 μCol/cm2/ph for 1000 h as follows: Group A: 1000 Hz, 100 μs/ph duration, 100 μA peak; Group B: 250 Hz, 100 μs/ph duration, 100 μA peak; Group C: 2750 Hz, 36 μs/ph duration, 250 μA peak; Group D: 250 Hz, 400 μs/ph duration, 25 μA peak. Also, two control groups received 20 min stimulation during weekly electrically evoked auditory brainstem response (eABR) measurement (Group E) and about 5 s stimulation (Group F) during a brief eABR 3 day postimplantation and at perfusion. On Day 50, animals were perfused, midmodiolar sections cut and a quantitative assessment of spiral ganglion cells (SGC) performed. All stimulated subjects showed a similar decrease in eABR thresholds and dynamic range over time. No stimulation conditions induced pathology. All stimulation conditions enhanced survival of SGCs compared to unimplanted ears and implanted non-stimulated ears (Group F). There were no statistically significant differences in SGC survival between any stimulated groups, including Group E stimulated once a week. In conclusion, high-rate stimulation, under the conditions of this study, provides no additional risks and the same benefits to SGC survival as low-rate stimulation.

Search for frequency-specific effects of millimeter-wave radiation on isolated nerve function.

Effects of a short-term exposure to millimeter waves (CW, 40-52 GHz, 0.24-3.0 mW/cm2) on the compound action potential (CAP) conduction were studied in an isolated frog sciatic nerve preparation. CAPs were evoked by either a low-rate or a high-rate electrical stimulation of the nerve (4 and 20 paired pulses/s, respectively). The low-rate stimulation did not alter the functional state of the nerve, and the amplitude, latency, and peak latency of CAPs could stay virtually stable for hours. Microwave irradiation for 10-60 min at 0.24-1.5 mW/cm2, either at various constant frequencies or with a stepwise frequency change (0.1 or 0.01 GHz/min), did not cause any detectable changes in CAP conduction or nerve refractoriness. The effect observed under irradiation at a higher field intensity of 2-3 mW/cm2 was a subtle and transient reduction of CAP latency and peak latency along with a rise of the test CAP amplitude. These changes could be evoked by any tested frequency of the radiation; they reversed shortly after cessation of exposure and were both qualitatively and quantitatively similar to the effect of conventional heating of 0.3-0.4 degree C. The high-rate electrical stimulation caused gradual and reversible decrease of the amplitude of conditioning and test CAPs and increased their latencies and peak latencies. These changes were essentially the same with and without irradiation (2.0-2.7 or 0.24-0.28 mW/cm2), except for attenuation of the decrease of the test CAP amplitude. This effect was observed at both field intensities, but was statistically significant only for certain frequencies of the radiation. Within the studied limits, this effect appeared to be dependent on the frequency rather than on the intensity of the radiation, but this observation requires additional experimental confirmation.

Effects of Hypothalamic Electrical Stimulation on the Urinary Testosterone Glycuronide in the Adult Male Rat

The influence of electrical stimulation of various hypothalamic areas on the urinary excretion of testosterone glycuronide (TG) was investigated in the awake, unrestrained, unanesthetized male rat. The urinary TG was determined by means of a gas chromatographic method. Either low-rate or high-rate electrical stimulation of paraventricular, suprachiasmatic and medial tuberal regions elicited a highly significant, short-lasting increase in the urinary TG excretion. No modification in the urinary TG excretion occurred after electrical stimulation of other brain formations as the cerebral cortex or the cerebellum.