Characterizing the relationship between modulation sensitivity and pitch resolution in cochlear implant users.

Cochlear implants are medical devices that have restored hearing to approximately one million people around the world. Outcomes are impressive and most recipients attain excellent speech comprehension in quiet without relying on lip-reading cues, but pitch resolution is poor compared to normal hearing. Amplitude modulation of electrical stimulation is a primary cue for pitch perception in cochlear implant users. The experiments described in this article focus on the relationship between sensitivity to amplitude modulations and pitch resolution based on changes in the frequency of amplitude modulations. In the first experiment, modulation sensitivity and pitch resolution were measured in adults with no known hearing loss and in cochlear implant users with sounds presented to and processed by their clinical devices. Stimuli were amplitude-modulated sinusoids and amplitude-modulated narrow-band noises. Modulation detection and modulation frequency discrimination were measured for modulation frequencies centered on 110, 220, and 440 Hz. Pitch resolution based on changes in modulation frequency was measured for modulation depths of 25 %, 50 %, 100 %, and for a half-waved rectified modulator. Results revealed a strong linear relationship between modulation sensitivity and pitch resolution for cochlear implant users and peers with no known hearing loss. In the second experiment, cochlear implant users took part in analogous procedures of modulation sensitivity and pitch resolution but bypassing clinical sound processing using single-electrode stimulation. Results indicated that modulation sensitivity and pitch resolution was better conveyed by single-electrode stimulation than by clinical processors. Results at 440 Hz were worse, but also not well conveyed by clinical sound processing, so it remains unclear whether the 300 Hz perceptual limit described in the literature is a technological or biological limitation. These results highlight modulation depth and sensitivity as critical factors for pitch resolution in cochlear implant users and characterize the relationship that should inform the design of modulation enhancement algorithms for cochlear implants.

Advantages of Pulse Rate Compared to Modulation Frequency for Temporal Pitch Perception in Cochlear Implant Users.

Most cochlear implants encode the fundamental frequency of periodic sounds by amplitude modulation of constant-rate pulsatile stimulation. Pitch perception provided by such stimulation strategies is markedly poor. Two experiments are reported here that consider potential advantages of pulse rate compared to modulation frequency for providing stimulation timing cues for pitch. The first experiment examines beat frequency distortion that occurs when modulating constant-rate pulsatile stimulation. This distortion has been reported on previously, but the results presented here indicate that distortion occurs for higher stimulation rates than previously reported. The second experiment examines pitch resolution as provided by pulse rate compared to modulation frequency. The results indicate that pitch discrimination is better with pulse rate than with modulation frequency. The advantage was large for rates near what has been suggested as the upper limit of temporal pitch perception conveyed by cochlear implants. The results are relevant to sound processing design for cochlear implants particularly for algorithms that encode fundamental frequency into deep envelope modulations or into precisely timed pulsatile stimulation.

Pitch perception is more robust to interference and better resolved when provided by pulse rate than by modulation frequency of cochlear implant stimulation.

Cochlear implants are medical devices that have been used to restore hearing to more than half a million people worldwide. Most recipients achieve high levels of speech comprehension through these devices, but speech comprehension in background noise and music appreciation in general are markedly poor compared to normal hearing. A key aspect of hearing that is notably diminished in cochlear implant outcomes is the sense of pitch provided by these devices. Pitch perception is an important factor affecting speech comprehension in background noise and is critical for music perception. The present article summarizes two experiments that examine the robustness and resolution of pitch perception as provided by cochlear implant stimulation timing. The driving hypothesis is that pitch conveyed by stimulation timing cues is more robust and better resolved when provided by variable pulse rates than by modulation frequency of constant-rate stimulation. Experiment 1 examines the robustness for hearing a large, one-octave, pitch difference in the presence of interfering electrical stimulation. With robustness to interference characterized for an otherwise easily discernible pitch difference, Experiment 2 examines the resolution of discrimination thresholds in the presence of interference as conveyed by modulation frequency or by pulse rate. These experiments test for an advantage of stimulation with precise temporal cues. The results indicate that pitch provided by pulse rate is both more robust to interference and is better resolved compared to when provided by modulation frequency. These results should inform the development of new sound processing strategies for cochlear implants designed to encode fundamental frequency of sounds into precise temporal stimulation.

Pleasantness Ratings of Musical Dyads in Cochlear Implant Users.

Cochlear implants have been used to restore hearing to more than half a million people around the world. The restored hearing allows most recipients to understand spoken speech without relying on visual cues. While speech comprehension in quiet is generally high for recipients, many complain about the sound of music. The present study examines consonance and dissonance perception in nine cochlear implant users and eight people with no known hearing loss. Participants completed web-based assessments to characterize low-level psychophysical sensitivities to modulation and pitch, as well as higher-level measures of musical pleasantness and speech comprehension in background noise. The underlying hypothesis is that sensitivity to modulation and pitch, in addition to higher levels of musical sophistication, relate to higher-level measures of music and speech perception. This hypothesis tested true with strong correlations observed between measures of modulation and pitch with measures of consonance ratings and speech recognition. Additionally, the cochlear implant users who were the most sensitive to modulations and pitch, and who had higher musical sophistication scores, had similar pleasantness ratings as those with no known hearing loss. The implication is that better coding and focused rehabilitation for modulation and pitch sensitivity will broadly improve perception of music and speech for cochlear implant users.

The PDE6 mutation in the rd10 retinal degeneration mouse model causes protein mislocalization and instability and promotes cell death through increased ion influx.

The retinal degeneration model rd10 contains a missense mutation of the catalytic PDE6 ß subunit, which hydrolyzes cGMP in response to light. This model produces cell death more slowly than others caused by PDE6 loss of function, making it of particular interest for studying potential therapeutics. We used morphology, biochemistry, and single-cell physiology to examine the mechanism of rd10 degeneration. Our results show that the mutation produces no alteration of Pde6b RNA but does dramatically decrease maximal and basal PDE6 activity, apparently caused by a decrease in protein stability and transport. The enzymatic properties of the remaining mutant PDE6 appear to be nearly normal. We demonstrate that an increase in free cGMP, which would result from decreased PDE6 activity and serve to increase opening of the cGMP-gated channels and calcium influx, is an underlying cause of cell death: degeneration of rd10/Cngb1-/- double mutants is slower than the parent rd10 line. Paradoxically, degeneration in rd10/Cngb1-/- is also slower than in Cngb1-/- This rescue is correlated with a lowering of cGMP content in Cngb1-/- retinas and suggests that it may be caused by mislocalization of active PDE6. Single-cell recordings from rd10 rods show that the rates of rise and decay of the response are significantly slower; simulations indicate that these changes are primarily the result of the decrease in PDE6 concentration and rod collecting area. Together, these results provide insights into the complex mechanisms that underlie rd10-mediated retinal degeneration and a cautionary note for analysis of therapeutic interventions.