Auditory Hypersensitivity and Processing Deficits in a Rat Model of Fragile X Syndrome

Fragile X (FX) syndrome is one of the leading inherited causes of autism spectrum disorder (ASD). A majority of FX and ASD patients exhibit sensory hypersensitivity, including auditory hypersensitivity or hyperacusis, a condition in which everyday sounds are perceived as much louder than normal. Auditory processing deficits in FX and ASD also afford the opportunity to develop objective and quantifiable outcome measures that are likely to translate between humans and animal models due to the well-conserved nature of the auditory system and well-developed behavioral read-outs of sound perception. Therefore, in this study we characterized auditory hypersensitivity in a Fmr1 knockout (KO) transgenic rat model of FX using an operant conditioning task to assess sound detection thresholds and suprathreshold auditory reaction time-intensity (RT-I) functions, a reliable psychoacoustic measure of loudness growth, at a variety of stimulus frequencies, bandwidths and durations. Male Fmr1 KO and littermate WT rats both learned the task at the same rate and exhibited normal hearing thresholds. However, Fmr1 KO rats had faster auditory RTs over a broad range of intensities and steeper RT-I slopes than WT controls, perceptual evidence of excessive loudness growth in Fmr1 KO rats. Furthermore, we found that Fmr1 KO animals exhibited abnormal perceptual integration of sound duration and bandwidth, with diminished temporal but enhanced spectral integration of sound intensity. Because temporal and spectral integration of sound stimuli were altered in opposite directions in Fmr1 KO rats, this suggests that abnormal RTs in these animals are evidence of aberrant auditory processing rather than generalized hyperactivity or altered motor responses. Together, these results are indicative of fundamental changes to low-level auditory processing in Fmr1 KO animals. Finally, we demonstrated that antagonism of metabotropic glutamate receptor 5 (mGlu5) selectively and dose-dependently restored normal loudness growth in Fmr1 KO rats, suggesting a pharmacologic approach for alleviating sensory hypersensitivity associated with FX. This study leverages the tractable nature of the auditory system and the unique behavioral advantages of rats to provide important insights into the nature of a centrally important yet understudied aspect of FX and ASD.

The Effect of Nonlinear Amplitude Growth on the Speech Perception Benefits Provided by a Single-Sided Vocoder

PurposeFor listeners with single-sided deafness, a cochlear implant (CI) can improve speech understanding by giving the listener access to the ear with the better target-to-masker ratio (TMR; head shadow) or by providing interaural difference cues to facilitate the perceptual separation of concurrent talkers (squelch). CI simulations presented to listeners with normal hearing examined how these benefits could be affected by interaural differences in loudness growth in a speech-on-speech masking task.MethodExperiment 1 examined a target–masker spatial configuration where the vocoded ear had a poorer TMR than the nonvocoded ear. Experiment 2 examined the reverse configuration. Generic head-related transfer functions simulated free-field listening. Compression or expansion was applied independently to each vocoder channel (power-law exponents: 0.25, 0.5, 1, 1.5, or 2).ResultsCompression reduced the benefit provided by the vocoder ear in both experiments. There was some evidence that expansion increased squelch in Experiment 1 but reduced the benefit in Experiment 2 where the vocoder ear provided a combination of head-shadow and squelch benefits.ConclusionsThe effects of compression and expansion are interpreted in terms of envelope distortion and changes in the vocoded-ear TMR (for head shadow) or changes in perceived target–masker spatial separation (for squelch). The compression parameter is a candidate for clinical optimization to improve single-sided deafness CI outcomes.

Patterns of Aided Loudness Growth in Experienced Adult Listeners with Early-Onset Severe–Profound Hearing Loss

Individuals with early-onset severe–profound bilateral hearing loss (S/PHL) manifest diverse levels of benefit and satisfaction with hearing aids (HAs), even with prescriptive HA fitting. Such fittings incorporate normal loudness values, but little is known about aided loudness outcomes in this population and how those outcomes affect benefit or satisfaction.To describe aided loudness growth and satisfaction with aided listening in experienced adult HA users with S/PHL.The Contour Test of loudness perception was administered to listeners with S/PHL in the aided sound field using broadband speech, band-limited speech, and warble tones. Patterns and slopes of resultant loudness growth functions were referenced to sound field results from listeners with normal hearing (NH). S/PHL listeners also rated their aided listening satisfaction. It was expected that (1) most S/PHL listeners would demonstrate steeper than normal aided loudness growth, (2) loudness normalization would be associated with better high-frequency detection thresholds and speech recognition, and (3) closer approximation to normal would yield greater satisfaction.Participants were paid college-student volunteers: 23 with S/PHL, long-term aided listening experience, and new HAs; 15 with NH.Participants rated loudness on four ascending runs per stimulus (5-dB increments) using categories defined in 1997 by Cox and colleagues. The region between the 10th and 90th percentiles of the NH distribution constituted local norms against which location and slope of the S/PHL functions were examined over the range from Quiet to Loud-but-OK. S/PHL functions were categorized on the basis of their configurations (locations/slopes) relative to the norms.Pattern of aided loudness was normalized or within 5 dB of the normal region on 37% of trials with sufficient data for analysis. Only one of the 23 S/PHL listeners did not demonstrate Normal/Near-normal loudness on any trials. Four nonnormal patterns were identified: Steep (recruitment-like; 38% of trials); Shifted right, with normal growth rate (10%); Hypersensitive, with most intensities louder than normal (10%); and Shallow, with decreasing growth rate (7%). Listeners with high-frequency average thresholds above 100 dB hearing loss or no phonemic-based speech-discrimination skill were less likely to display normalized loudness. Slope was within norms for 52% of S/PHL trials, most also having a Normal/Near-normal growth pattern. Regardless of measured loudness results, all but four listeners with S/PHL reported satisfactory hearing almost always or most of the time with their HAs in designated priority need areas.The variety of aided loudness growth patterns identified reflects the diversity known to characterize individuals with early-onset S/PHL. Loudness rating at the validation stage of HA fit with these listeners is likely to reveal nonnormal loudness, signaling need for further HA adjustment. High satisfaction, however, despite nonnormal loudness growth, suggests that listeners with poor auditory speech recognition may benefit more from aided loudness that supports pattern perception (via the time-intensity waveform of speech), different from most current-day prescription fits.