Scott K. Griffiths

The perception of speech sounds recorded within the uterus of a pregnant sheep

The intelligibility of speech stimuli recorded within the uterus of a pregnant sheep was determined perceptually using a group of untrained judges. The intrauterine sound environment of the ewe was intended to simulate that of a pregnant woman. Two separate lists, one of meaningful and one of nonmeaningful speech stimuli, were delivered through a loudspeaker to the side of the ewe and were simultaneously recorded with an air microphone located 15 cm from the flank and with a hydrophone previously sutured to the neck of the fetus. Perceptual test tapes generated from these recordings were played to 102 judges. The intelligibility of the phonemes recorded in the air was significantly greater than the intelligibility of phonemes recorded from the uterus. A male talkers voice was more intelligible than a female talkers voice when recorded from within the uterus, but not so when recorded in the air. An analysis of the feature information transmission from recordings inside and outside the uterus revealed that voicing information is better transmitted in utero than place or manner information.

The amplitude-modulation-following response as an audiometric tool

The amplitude modulation-following response (AMFR) is an auditory scalp-recorded potential, evoked using continuous, amplitude-modulated tones. The current study was designed to explore the audiometric utility of the AMFR by demonstrating the frequency specificity of the response and assessing the relation between behaviorally measured pure-tone thresholds and AMFR detection thresholds. Subjects in this study were six normal-hearing and four hearing-impaired adults. High-pass masking results in the normal hearing subjects demonstrated that the AMFR is associated with a narrow range of activation along the cochlea around the carrier frequency. Frequency-specific results from the hearing-impaired subjects confirmed this finding. Thresholds for the AMFR, defined in spectral terms, were consistent with the behavioral estimates in both the normal and the hearing-impaired subjects.

Effects of age on the adult auditory middle latency response

The middle latency components of the auditory evoked response were obtained from a group of normal-hearing, healthy female subjects from 22 to 68 years of age. Recordings were made at several intensity levels to assess the level-dependence of any age-related effects. Cross-sectional analyses revealed that the amplitude of component Pa grows linearly with age, becoming significantly larger in older (50-68 years of age) compared to younger (22-37 years) subjects. The amplitude-intensity function is steeper in the older subjects by a factor of two. Correlational analyses suggested that at higher intensity levels age accounts for about 20% of the variance in the amplitude of Pa. A positive shift in response baseline was observed in the older subjects, and could contribute to the age-related increase in the absolute amplitude of Pa. However, a similar increase in the peak-to-peak and area measures of Pa suggests that some of the increase in the magnitude of Pa is independent of baseline shift. A confounding of age and hearing sensitivity in this study makes it difficult to interpret the age-related effects as strictly central in nature.

Intelligibility of Sentences Recorded from the Uterus of a Pregnant Ewe and from the Fetal Inner Ear

The intelligibility of sentences recorded from the uterus of a pregnant ewe and from the near-term fetal sheep inner ear was judged by 30 listeners. Sentences were presented to the ewe at 95 and 105 dB SPL while sequential recordings of sound with a hydrophone and a cochlear microphonic (CM) with electrodes were made. Recordings were randomized and presented to listeners to judge the intelligibility of sentences processed through the ewe and fetal inner ear. Intelligibility scores were nearly 99% for air and uterus conditions, dropped to 73% for CM ex utero and to 41% for CM in utero. Results indicated that filtering provided by the tissues and fluids of the maternal abdomen did not affect sentence intelligibility significantly, but the filtering effects as the signal passed into the fetal inner ear resulted in much poorer intelligibility.

Fetal Music Perception: The Role of Sound Transmission

The fetal sound environment is now known to be rich and varied. Playback of tapes made from intrauterine recordings of sounds reveals some muffling, suggesting an attenuation of high-frequency sounds at the surface of the abdominal wall and during transmission through abdominal and uterine tissues and fluids. The present experiments show how the spectral features of synthesized musical sounds are altered once they reach the ear of the fetal sheep. Below 300 Hz, intrauterine sound pressure levels are nearly identical to those recorded outside the ewe. Between 315 and 2500 Hz, the attenuation increases at a rate of 5 dB per octave. Spectral analyses of trumpet and flugelhorn sounds recorded in utero show a marked diminution in sound pressure level in partials above 600 Hz; this diminution could be perceived by the fetus as an altered timbre.

Noise induced hearing loss in fetal sheep

The auditory brainstem response (ABR) was recorded in utero from chronically instrumented fetal sheep prior to and following exposure of pregnant ewes to intense broadband noise (120 dB SPL for 16 h). ABRs were elicited by clicks and tone bursts (0.5, 1, 2, and 4 kHz) delivered through a bone oscillator secured to the fetal skull. Latency-intensity functions for most of the four vertex-positive waves (labelled I-IV) were prolonged and ABR thresholds were temporarily elevated by an average of 8 dB following the noise exposure. Results show that exogenous sounds can penetrate the uterus and result in alterations of the fetal ABR.

Safety and efficacy of ebselen for the prevention of noise-induced hearing loss: a randomised, double-blind, placebo-controlled, phase 2 trial

BACKGROUND Noise-induced hearing loss is a leading cause of occupational and recreational injury and disease, and a major determinant of age-related hearing loss. No therapeutic agent has been approved for the prevention or treatment of this disorder. In animal models, glutathione peroxidase 1 (GPx1) activity is reduced after acute noise exposure. Ebselen, a novel GPx1 mimic, has been shown to reduce both temporary and permanent noise-induced hearing loss in preclinical studies. We assessed the safety and efficacy of ebselen for the prevention of noise-induced hearing loss in young adults in a phase 2 clinical trial. METHODS In this single-centre, randomised, double-blind, placebo-controlled phase 2 trial, healthy adults aged 18-31 years were randomly assigned (1:1:1:1) at the University of Florida (Gainsville, FL, USA) to receive ebselen 200 mg, 400 mg, or 600 mg, or placebo orally twice daily for 4 days, beginning 2 days before a calibrated sound challenge (4 h of pre-recorded music delivered by insert earphones). Randomisation was done with an allocation sequence generated by an independent third party. The primary outcome was mean temporary threshold shift (TTS) at 4 kHz measured 15 min after the calibrated sound challenge by pure tone audiometry; a reduction of 50% in an ebselen dose group compared with the placebo group was judged to be clinically relevant. All participants who received the calibrated sound challenge and at least one dose of study drug were included in the efficacy analysis. All randomly assigned patients were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT01444846. FINDINGS Between Jan 11, 2013, and March 24, 2014, 83 participants were enrolled and randomly assigned to receive ebselen 200 mg (n=22), 400 mg (n=20), or 600 mg (n=21), or placebo (n=20). Two participants in the 200 mg ebselen group were discontinued from the study before the calibrated sound challenge because they no longer met the inclusion criteria; these participants were excluded from the efficacy analysis. Mean TTS at 4 kHz was 1·32 dB (SE 0·91) in the 400 mg ebselen group compared with 4·07 dB (0·90) in the placebo group, representing a significant reduction of 68% (difference -2·75 dB, 95% CI -4·54 to -0·97; p=0·0025). Compared with placebo, TTS at 4 kHz was non-significantly reduced by 21% in the 200 mg ebselen group (3·23 dB [SE 0·91] vs 4·07 dB [0·90] in the placebo group; difference -0·84 dB, 95% CI -2·63 to 0·94; p=0·3542) and by 7% in the 600 mg ebselen group (3·81 dB [0·90] vs 4·07 dB [0·90] in the placebo group; difference -0·27, 95% CI -2·03 to 1·50; p=0·7659). Ebselen treatment was well tolerated across all doses and no significant differences were seen in any haematological, serum chemistry, or radiological assessments between the ebselen groups and the placebo group. INTERPRETATION Treatment with ebselen was safe and effective at a dose of 400 mg twice daily in preventing a noise-induced TTS. These data lend support to a role of GPx1 activity in acute noise-induced hearing loss. FUNDING Sound Pharmaceuticals.

Temporary threshold shift after impulse-noise during video game play: laboratory data.

Abstract Objective: Prevention of temporary threshold shift (TTS) after laboratory-based exposure to pure-tones, broadband noise, and narrowband noise signals has been achieved, but prevention of TTS under these experimental conditions may not accurately reflect protection against hearing loss following impulse noise. This study used a controlled laboratory-based TTS paradigm that incorporated impulsive stimuli into the exposure protocol; development of this model could provide a novel platform for assessing proposed therapeutics. Design: Participants played a video game that delivered gunfire-like sound through headphones as part of a target practice game. Effects were measured using audiometric threshold evaluations and distortion product otoacoustic emissions (DPOAEs). The sound level and number of impulses presented were sequentially increased throughout the study. Study sample: Participants were normal-hearing students at the University of Florida who provided written informed consent prior to participation. Results: TTS was not reliably induced by any of the exposure conditions assessed here. However, there was significant individual variability, and a subset of subjects showed TTS under some exposure conditions. Conclusions: A subset of participants demonstrated reliable threshold shifts under some conditions. Additional experiments are needed to better understand and optimize stimulus parameters that influence TTS after simulated impulse noise.

Correlations between various measures of head size and auditory brainstem response latencies

The literature is mixed concerning the degree to which between-subject variance in the latencies of the auditory brainstem response (ABR) relates to differences in the length of the auditory pathway. Most investigations have used one of several measures of head size to indirectly index brain size and neural pathway length. While some studies have found a positive correlation between head size and the latencies of the ABR, others have reported little or no relationship. We hypothesized that the differences between studies result from differences in the head dimensions measured, the precision of measurement technique, and issues of sampling. We therefore decided to use the International 10-20 system of electrode placement to provide reproducible skull benchmarks on which to base head size measures, to obtain measures of head size via two procedures, and to control external variables that might influence the ABR. The results show that head size has a moderate positive influence on the latencies of the ABR given precise head size measures.

Transmission of airborne sound from 50-20,000 Hz into the abdomen of sheep

The transmission of audible sounds from the environment of the pregnant woman to the foetus is of growing interest to obstetricians who utilize foetal vibracoustic stimulation in their examinations, and to occupational health professionals who believe that high-intensity sound in the workplace is potentially damaging to the foetus. Earlier reports on transmission of sound into the abdomen and uterus of sheep revealed a significant amount of sound attenuation at frequencies above 2,000 Hz. and some enhancement at frequencies below 250 Hz. However, frequencies above 10,000 Hz, and stimulus levels as possible variables, were not studied. In this report, the effects of frequency from 50-20,000 Hz. and stimulus levels (90 to 110 dB sound pressure level), were studied in five sheep. Sound attenuation varied as a function of frequency (p<0.001). Sound attenuation varied inversely as a function of stimulus level for low frequencies (50-125 Hz) and for high frequencies (7,000–20,000 Hz) (p<0.001). In the mid frequency range (200-4,000 Hz), no effect of stimulus level (p=0.96) was found. Additionally, in the 800-2,000 Hz range there was enhancement of sound pressure of up to 10 dB.