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Distortion-product otoacoustic emission suppression tuning curves in humans.

ABSTRACT: Distortion-product otoacoustic emission (DPOAE) suppression data as a function of suppressor level (L(3)) for f(2) frequencies from 0.5 to 8 kHz and L(2) levels from 10 to 60 dB sensation level were used to construct suppression tuning curves (STCs). DPOAE levels in the presence of suppressors were converted into decrement versus L(3) functions, and the L(3) levels resulting in 3 dB decrements were derived by transformed linear regression. These L(3) levels were plotted as a function of f(3) to construct STCs. When f(3) is represented on an octave scale, STCs were similar in shape across f(2) frequency. These STCs were analyzed to provide estimates of gain (tip-to-tail difference) and tuning (Q(ERB)). Both gain and tuning decreased as L(2) increased, regardless of f(2), but the trend with f(2) was not monotonic. A roughly linear relation was observed between gain and tuning at each frequency, such that gain increased by 4-16 dB (mean ≈ 5 dB) for every unit increase in Q(ERB), although the pattern varied with frequency. These findings suggest consistent nonlinear processing across a wide frequency range in humans, although the nonlinear operation range is frequency dependent.

SUBMITTER: Gorga MP

PROVIDER: S-EPMC3070996 | biostudies-other | 2011 Feb

REPOSITORIES: biostudies-other

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Project description:BackgroundAlthough several candidate-gene association studies have been conducted to investigate noise-induced hearing loss (NIHL) in humans, most are underpowered, unreplicated, and account for only a fraction of the genetic risk. Mouse genome-wide association studies (GWASs) have revolutionized the field of genetics and have led to the discovery of hundreds of genes involved in complex traits. The hybrid mouse diversity panel (HMDP) is a collection of classic inbred and recombinant inbred strains whose genomes have been either genotyped at high resolution or sequenced. To further investigate the genetics of NIHL, we report the first GWAS based on distortion product otoacoustic emission (DPOAE) measurements and the HMDP.MethodsA total of 102 strains (n = 635) from the HMDP were evaluated based on DPOAE suprathreshold amplitudes before and after noise exposure. DPOAE amplitude variation was set at 60 and 70 dB SPL of the primary tones for each frequency separately (8, 11.3, 16, 22.6, and 32 kHz). These values provided an indirect assessment of outer hair cell integrity. Six-week-old mice were exposed for 2 h to 10 kHz octave-band noise at 108 dB SPL. To perform local expression quantitative trait locus (eQTL) analysis, gene expression microarray profiles were generated using cochlear RNA from 64 hybrid mouse strains (n = 3 arrays per strain).ResultsSeveral new loci were identified and positional candidate-genes associated with NIHL were prioritized, especially after noise exposure (1 locus at baseline and 5 loci after exposure). A total of 35 candidate genes in these 6 loci were identified with at least 1 probe whose expression was regulated by a significant cis-eQTL in the cochlea. After careful analysis of the candidate genes based on cochlear gene expression, 2 candidate genes were prioritized: Eya1 (baseline) and Efr3a (post-exposure).Discussion and conclusionFor the first time, an association analysis with correction for population structure was used to map several loci for hearing traits in inbred strains of mice based on DPOAE suprathreshold amplitudes before and after noise exposure. Our results identified a number of novel loci and candidate genes for susceptibility to NIHL, especially the Eya1 and Efr3a genes. Our findings validate the power of the HMDP for detecting NIHL susceptibility genes.

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Distortion-product otoacoustic emission suppression tuning curves in humans.

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