Individual differences in supra-threshold auditory perception - mechanisms and objective correlates

Thesis (Ph.D.)--Boston UniversityTo extract content and meaning from a single source of sound in a quiet background, the auditory system can use a small subset of a very redundant set of spectral and temporal features. In stark contrast, communication in a complex, crowded scene places enormous demands on the auditory system. Spectrotemporal overlap between sounds reduces modulations in the signals at the ears and causes masking, with problems exacerbated by reverberation. Consistent with this idea, many patients seeking audiological treatment seek help precisely because they notice difficulties in environments requiring auditory selective attention. In the laboratory, even listeners with normal hearing thresholds exhibit vast differences in the ability to selectively attend to a target. Understanding the mechanisms causing these supra-threshold differences, the focus of this thesis, may enable research that leads to advances in treating communication disorders that affect an estimated one in five Americans. Converging evidence from human and animal studies points to one potential source of these individual differences: differences in the fidelity with which supra-threshold sound is encoded in the early portions of the auditory pathway. Electrophysiological measures of sound encoding by the auditory brainstem in humans and animals support the idea that the temporal precision of the early auditory neural representation can be poor even when hearing thresholds are normal. Concomitantly, animal studies show that noise exposure and early aging can cause a loss (cochlear neuropathy) of a large percentage of the afferent population of auditory nerve fibers innervating the cochlear hair cells without any significant change in measured audiograms. Using behavioral, otoacoustic and electrophysiological measures in conjunction with computational models of sound processing by the auditory periphery and brainstem, a detailed examination of temporal coding of supra-threshold sound is carried out, focusing on characterizing and understanding individual differences in listeners with normal hearing thresholds and normal cochlear mechanical function. Results support the hypothesis that cochlear neuropathy may reduce encoding precision of supra-threshold sound, and that this manifests as deficits both behaviorally and in subcortical electrophysiological measures in humans. Based on these results, electrophysiological measures are developed that may yield sensitive, fast, objective measures of supra-threshold coding deficits that arise as a result of cochlear neuropathy

Individual Differences Reveal Correlates of Hidden Hearing Deficits

Clinical audiometry has long focused on determining the detection thresholds for pure tones, which depend on intact cochlear mechanics and hair cell function. Yet many listeners with normal hearing thresholds complain of communication difficulties, and the causes for such problems are not well understood. Here, we explore whether normal-hearing listeners exhibit such suprathreshold deficits, affecting the fidelity with which subcortical areas encode the temporal structure of clearly audible sound. Using an array of measures, we evaluated a cohort of young adults with thresholds in the normal range to assess both cochlear mechanical function and temporal coding of suprathreshold sounds. Listeners differed widely in both electrophysiological and behavioral measures of temporal coding fidelity. These measures correlated significantly with each other. Conversely, these differences were unrelated to the modest variation in otoacoustic emissions, cochlear tuning, or the residual differences in hearing threshold present in our cohort. Electroencephalography revealed that listeners with poor subcortical encoding had poor cortical sensitivity to changes in interaural time differences, which are critical for localizing sound sources and analyzing complex scenes. These listeners also performed poorly when asked to direct selective attention to one of two competing speech streams, a task that mimics the challenges of many everyday listening environments. Together with previous animal and computational models, our results suggest that hidden hearing deficits, likely originating at the level of the cochlear nerve, are part of “normal hearing.

Cochlear neuropathy and the coding of supra-threshold sound

Many listeners with hearing thresholds within the clinically normal range nonetheless complain of difficulty hearing in everyday settings and understanding speech in noise. Converging evidence from human and animal studies points to one potential source of such difficulties: differences in the fidelity with which supra-threshold sound is encoded in the early portions of the auditory pathway. Measures of auditory subcortical steady-state responses (SSSRs) in humans and animals support the idea that the temporal precision of the early auditory representation can be poor even when hearing thresholds are normal. In humans with normal hearing thresholds (NHTs), paradigms that require listeners to make use of the detailed spectro-temporal structure of supra-threshold sound, such as selective attention and discrimination of frequency modulation (FM), reveal individual differences that correlate with subcortical temporal coding precision. Animal studies show that noise exposure and aging can cause a loss of a large percentage of auditory nerve fibers (ANFs) without any significant change in measured audiograms. Here, we argue that cochlear neuropathy may reduce encoding precision of supra-threshold sound, and that this manifests both behaviorally and in SSSRs in humans. Furthermore, recent studies suggest that noise-induced neuropathy may be selective for higher-threshold, lower-spontaneous-rate nerve fibers. Based on our hypothesis, we suggest some approaches that may yield particularly sensitive, objective measures of supra-threshold coding deficits that arise due to neuropathy. Finally, we comment on the potential clinical significance of these ideas and identify areas for future investigation

Isoniazid concentrations in hair and plasma area-under-the-curve exposure among children with tuberculosis.

We measured hair and plasma concentrations of isoniazid among sixteen children with tuberculosis who underwent personal or video-assisted directly observed therapy and thus had 100% adherence. This study therefore defined typical isoniazid exposure parameters after two months of treatment among fully-adherent patients in both hair and plasma (plasma area under the concentration-time curve, AUC, estimated using pharmacokinetic data collected 0, 2, 4, and 6 hours after drug administration). We found that INH levels in hair among highly-adherent individuals did not correlate well with plasma AUC or trough concentrations, suggesting that each measure may provide incremental and complementary information regarding drug exposure in the context of TB treatment