Distortion Product Amplitudes Research Articles

Serum Prestin Level May Increase Following Music Exposure That Induces Temporary Threshold Shifts: A Pilot Study.

To determine if blood prestin level changes after exposure to music at high sound pressure levels, and if this change is associated with temporary threshold shift (TTS) and/or changes in distortion product (DP) amplitude. Participants were exposed to pop-rock music at 100 dBA for 15 min monaurally through headphones. Pure-tone audiometry, DP amplitude, and blood prestin level were measured before and after exposure. Fourteen adults (9 women; age range: 20 to 54 years, median age = 31 [Interquartile ratio = 6.75]) with normal hearing were included in the study. Mean prestin level increased shortly after exposure to music, then returned to baseline within 1 week, although this trend was not observed in all participants. All participants presented TTS or a decrease in DP amplitude in at least one frequency after music exposure. There was a statistically significant average threshold elevation at 4 min postexposure. Statistically significant DP amplitude shifts were observed at 4 and 6 kHz, 2 min following exposure. Mean baseline serum prestin level (mean: 140.00 pg/mL, 95% confidence interval (CI): 125.92 to 154.07) progressively increased following music exposure, reaching a maximum at 2 hr (mean: 158.29 pg/mL, 95% CI: 130.42 to 186.66) and returned to preexposure level at 1 week (mean: 139.18 pg/mL, 95% CI: 114.69 to 163.68). However, after correction for multiple comparisons, mean prestin level showed no statistically significant increase from baseline at any timepoint. No correlation between maximum blood prestin level change and average TTS or distortion product otoacoustic emission amplitude shift was found. However, in an exploratory analysis, TTS at 6 kHz (the frequency at which maximum TTS occurred) decreased significantly as baseline blood prestin level increased. The results suggest that blood prestin level may change after exposure to music at high sound pressure levels, although statistical significance was not reached in this relatively small sample after correction. Baseline serum prestin level may also predict the degree of TTS. These findings thus suggest that the role of baseline serum prestin level as a proxy marker of cochlear susceptibility to intense music exposure should be further explored.

Studying of Distortion Product of Otoacoustic Emissions in Menopausal Women.

The sex hormones; estrogen and progesterone have a direct effect on the mechanisms of the inner cochlea and they control the functions of the ascending auditory pathway from the auditory nerve to the cerebral cortex. Therefore, the aim of this study was to determine the amplitude of distortion product of otoacoustic emissions (DPOAE) in postmenopausal women. This cross-sectional case-control study included 60 women who were naturally menopausal and were in the age range of 55 - 45 years (case group). The other 60 included women of the same age and non-menopause (control group). Both groups were selected from individuals who had normal auditory function based on pure tone audiometry, immitance audiometry (tympanometry + ipsilateral and contralateral reflex), speech tests and auditory brainstem responses. Then both groups were evaluated by DPOAE and its findings were analyzed in two groups based on independent t-test and the significance level of the test was determined to be less than 0.05. The difference between the mean DPOAE domains in the two groups was not significant (P-value = 0.484). Menopause is not an etiological factor to be created of abnormalities in the cochlea of ​​the inner ear. The online version contains supplementary material available at 10.1007/s12070-022-03210-1.

Contrasting Effects of Pressure Compensation on TEOAE and DPOAE in Children With Negative Middle Ear Pressure

In children with normal cochlear acuity, middle ear fluid often abolishes otoacoustic emissions (OAEs), and negative middle ear pressure (NMEP) reduces them. No convincing evidence of beneficial pressure compensation on distortion product OAE (DPOAE) has yet been presented. Two studies aimed to document effects of NMEP on transient OAE (TEOAE) and DPOAE. In Study 1, TEOAE and DPOAE pass/fail responses were analyzed before and after pressure compensation in 50 consecutive qualifying referrals having NMEP from −100 to −299 daPa. Study 2 concentrated on DPOAE, recording both amplitude (distortion product amplitude) and signal-to-noise ratio (SNR) before and after pressure compensation. Of the 20 participants, 5 had both ears qualifying. An effect of compensation on meeting a pass criterion was present in TEOAE for both left and right ear data in Study 1 but not demonstrable in DPOAE. In Study 2, the distortion product amplitude compensation effect was marginal overall, and depended on recording frequency band. SNR values improved moderately after pressure compensation in the two (overlapping) sets of single-ear data. In the five cases with both ears qualifying, a stronger compensation effect size, over 3 dB, was seen. The absolute dependence of SNR on frequency was also strongly replicated, but in no analysis, the frequency × compensation interaction was significant. Independent of particular frequency range, the data support a limited SNR improvement in 2 to 3 dB for compensation in DPOAE, with slightly larger effects in ears giving SNRs between 0 dB and +6 dB, where pass/fail cutoffs would generally be located.

N-acetylcysteine Treatment Reduces Age-related Hearing Loss and Memory Impairment in the Senescence-Accelerated Prone 8 (SAMP8) Mouse Model

Age-related hearing loss (ARHL) is the most common sensory disorder in the elderly population. SAMP8 mouse model presents accelerated senescence and has been identified as a model of gerontological research. SAMP8 displays a progressive age-related decline in brain function associated with a progressive hearing loss mimicking human aging memory deficits and ARHL. The molecular mechanisms associated with SAMP8 senescence process involve oxidative stress leading to chronic inflammation and apoptosis. Here, we studied the effect of N-acetylcysteine (NAC), an antioxidant, on SAMP8 hearing loss and memory to determine the potential interest of this model in the study of new antioxidant therapies. We observed a strong decrease of auditory brainstem response thresholds from 45 to 75 days of age and an increase of distortion product amplitudes from 60 to 75 days in NAC treated group compared to vehicle. Moreover, NAC treated group presented also an increase of memory performance at 60 and 105 days of age. These results confirm that NAC delays the senescence process by slowing the age-related hearing loss, protecting the cochlear hair cells and improving memory, suggesting that antioxidants could be a pharmacological target for age-related hearing and memory loss.

The relation between cochlear distortion products and frequency tuning characteristics revealed by laser interferometery

Objective:To explore the relation between distortion products and frequency tuning charateristics in cochlear basilar membrane.Method:Time variances curves of distortion products and frequency tuning curves of basilar membrane response were measured by laser interferometery in situ guinea pig cochlea.Result:Response sensitivity and tuning sharpness of basilar membrane response decreased with distortion product amplitude and become most low and flat when distortion products disappeared.Conclusion:Distortion products in cochlea are related with hearing sensitivity and frequency tuning. They are indicator whether function of cochlear hearing sensitivity enhancing and frequency tuning sharpening is still at work.

Senescence-accelerated mouse prone 8 (SAMP8) as a model of age-related hearing loss.

Hearing loss is the most common form of sensory impairment in humans, affecting 5.3% worldwide population. In industrial countries, age-related hearing loss is a major health problem affecting one-third of individuals over 65years old. However, the physiological and molecular changes involved in this senescence process remain unclear. In this study, we determined the influence of age on auditory brainstem response (ABR) and the distortion product otoacoustic emissions (DPOAE) in the premature senescence mouse model SAMP8 for five months. We showed a progressive increase of ABR thresholds and a decrease of distortion product amplitude from 37days old in SAMP8 compared to CBA mice. The data we show here provide new knowledge in functional auditory changes during the senescence process and open up new opportunities for the development of new drugs involved in age-related hearing loss treatment.

Distortion products in auditory fMRI research: Measurements and solutions

Nonlinearities in the cochlea can introduce audio frequencies that are not present in the sound signal entering the ear. Known as distortion products (DPs), these added frequencies complicate the interpretation of auditory experiments. Sound production systems also introduce distortion via nonlinearities, a particular concern for fMRI research because the Sensimetrics earphones widely used for sound presentation are less linear than most high-end audio devices (due to design constraints). Here we describe the acoustic and neural effects of cochlear and earphone distortion in the context of fMRI studies of pitch perception, and discuss how their effects can be minimized with appropriate stimuli and masking noise. The amplitude of cochlear and Sensimetrics earphone DPs were measured for a large collection of harmonic stimuli to assess effects of level, frequency, and waveform amplitude. Cochlear DP amplitudes were highly sensitive to the absolute frequency of the DP, and were most prominent at frequencies below 300Hz. Cochlear DPs could thus be effectively masked by low-frequency noise, as expected. Earphone DP amplitudes, in contrast, were highly sensitive to both stimulus and DP frequency (due to prominent resonances in the earphone's transfer function), and their levels grew more rapidly with increasing stimulus level than did cochlear DP amplitudes. As a result, earphone DP amplitudes often exceeded those of cochlear DPs. Using fMRI, we found that earphone DPs had a substantial effect on the response of pitch-sensitive cortical regions. In contrast, cochlear DPs had a small effect on cortical fMRI responses that did not reach statistical significance, consistent with their lower amplitudes. Based on these findings, we designed a set of pitch stimuli optimized for identifying pitch-responsive brain regions using fMRI. These stimuli robustly drive pitch-responsive brain regions while producing minimal cochlear and earphone distortion, and will hopefully aid fMRI researchers in avoiding distortion confounds.

Do antithyroid antibodies affect hearing outcomes in patients with pediatric euthyroid Hashimoto's thyroiditis?

ObjectivesHashimoto's thyroiditis (HT) is the most common autoimmune thyroid disease in children. HT is a multifaceted disease with a variable clinicopathological presentation, including hearing impairment. It is known that hearing function is negatively affected in patients with thyroid disorders. The literature includes a very limited number of studies on hearing function in euthyroid pediatric patients with HT. The aim of this study was to determine the relationship between cochlear function and HT, independent of thyroid function. Materials and MethodsThe study included 48 children and adolescents (42 females and 6 males) aged 9–18 years that were diagnosed as HT, and 30 gender- and age-matched healthy controls. Hearing was assessed via otoscopy, tympanometry, pure-tone audiometry, and measurement of distortion product otoacoustic emissions. ResultsThere weren't any significant differences in pure tone thresholds between the 2 groups based on pure-tone audiometry, except in the right ear at 6kHz and 8kHz. Distortion product otoacoustic emissions signal to noise ratios were significantly lower in the HT group than in the control group at 4 different frequencies (6kHz [left ear], 8kHz [left ear], 1.5kHz [right ear], and 6kHz [right ear]) (P<0.05). The signal to noise ratios at all frequencies were <6dB in 3% of left ears and 2.5% of right ears in the control group, versus 12.5% of left ears and 9.6% of right ears in the HT group. Distortion product amplitudes were significantly lower in the HT group than in the control group for both left and right ears at 1kHz, 1.5kHz, 3kHz, and 8kHz, and at 2kHz for left ears only (P<0.05). ConclusionsThe present findings show that cochlear function was lower in the HT group than in the control group. Accordingly, we think that hearing in patients with HT should be monitored periodically, even if their hearing thresholds are within normal limits. Thyroid autoimmunity appears to play an important role in a decrease in cochlear activity in pediatric HT patients.

Hearing screening in community centers for the elderly: Efficacy of distortion product otoacoustic emissions

Hearing loss occurs most frequently within the elderly population, and having a hearing loss can adversely impact the quality of life of an individual. There is a need for detection of hearing loss at an early stage, and therefore elderly hearing screening programs are important. The efficacy of using distortion product otoacoustic emissions (DPOAEs) as a stand-alone objective hearing screening tool in comparison to conventional, behavioral pure-tone screening in community centers for the elderly in Hong Kong was investigated. Background noise was measured at each center, and the range of overall noise levels was from 42 to 53 dBA. DPOAE results were analyzed using six different pass/refer criteria, having stimuli concentration in the low, mid, or high frequencies, and based upon both absolute distortion product amplitude and signal-to-noise ratio (SNR; stricter criterion) or SNR alone (looser criterion). Kappa statistics of weighted agreement and observed agreement were calculated to compare DPOAE measures with pure-tone screening for 223 elderly participants. The highest observed agreement between pure-tone screening and DPOAE was found for a protocol with a focus on mid-frequency stimuli using a looser criterion. However, the highest agreement obtained was only fair, with agreement occurring at only 14% more than chance. Background noise in community centers for the elderly adversely affected the DPOAE measurements and DPOAE screening could not be considered as an effective stand-alone hearing screening tool for an elderly population attending urban community centers.

Cisplatin-induced Ototoxicity Is Mediated by Nitroxidative Modification of Cochlear Proteins Characterized by Nitration of Lmo4

Tyrosine nitration is an important sequel of cellular signaling induced by reactive oxygen species. Cisplatin is an anti-neoplastic agent that damages the inner ear through reactive oxygen species and by the formation of DNA adducts. This study reveals a correlation between cisplatin-mediated hearing loss and nitroxidative modification of cochlear proteins and is the first to report nitration of Lmo4. Cisplatin induced a dose-dependent increase in hearing loss in Wistar rats. A 10-15-dB decrease in distortion product amplitude and massive loss of outer hair cells at the basal turn of the cochlea was observed 3 days post-treatment after a 16 mg/kg dose. Cisplatin induced nitration of cellular proteins within the organ of Corti, spiral ganglion, and stria vascularis, which are known targets of cisplatin ototoxicity. Nitration of a 76-kDa cochlear protein correlated with cisplatin dose. The nitrated protein was identified as Lmo4 (LIM domain only 4) by MALDI-TOF (matrix-assisted laser desorption/ionization time of flight) mass spectrometry and confirmed by reciprocal immunoprecipitation and immunoblotting. Co-localization of nitrotyrosine and Lmo4 was particularly high in outer hair cell nuclei after cisplatin treatment. Cochlear levels of Lmo4 were decreased in rats treated with cisplatin. In vitro studies supported the repression of Lmo4 in nitroxidative conditions and the induction of apoptosis upon repression of Lmo4. Inhibition of cochlear protein nitration prevented cisplatin-induced hearing loss. As Lmo4 is a transcriptional regulator that controls the choice between cell survival and cell death, these results support the hypothesis that nitration of Lmo4 influences cisplatin-induced ototoxicity.

The effect of resveratrol on the prevention of cisplatin ototoxicity

One of the most important adverse effects of cisplatin, a chemotherapeutic agent which is widely used in the treatment of cancer patients, is hearing loss. This has primarily been associated with the loss of inner ear hairy and spiral ganglion cells due to oxidative stress. Resveratrol is known to be an antioxidant agent, which has the theoretical potential of preventing cisplatin-related ototoxicity. This experimental study was approved by Animal Ethics Committee of Inonu University (2008-20) and supported by Inonu University Scientific Research Projects Support Fund (2009-17). Thirty-four 3-month-old Wistar albino female rats weighing 210-270 g were used in the study. The animals were allocated into four groups: in cisplatin group (Group A), a single dose of 12 mg/kg cisplatin was administered intraperitoneally to 10 rats; in cisplatin + resveratrol group (Group B), a single dose of 12 mg/kg cisplatin and 10 mg/kg resveratrol were administered intraperitoneally for 5 days to 10 rats; in resveratrol group (Group C), 10 mg/kg resveratrol was administered intraperitoneally for 5 days to seven rats and in control group (Group D), resveratrol solvent (5% alcohol-95% physiological saline) was administered intraperitoneally for 5 days to seven rats. Resveratrol administration has begun 1 day before cisplatin administration in the group treated with cisplatin and resveratrol combination. Distortion product otoacoustic emission (DPOAE) (Grason Stadler, Madison, USA) measurements were performed in the same ear of all rats (right ear) under general anesthesia at baseline, 1st and 5th days after drug administration. Statistically significant distortion product amplitude reductions were found in the cisplatin group at 1,418, 2,003, 3,363, 5,660, 8,003 and 9,515 Hz frequencies. Whereas in the cisplatin + resveratrol group, statistically significant difference was found between 1st and 5th day measurements only at 3,996 Hz frequency. No significant differences were noted between the measurements either in the resveratrol or in the control groups. According to these results, cisplatin-related ototoxicity has been greatly prevented by resveratrol use.

Otoacoustic emissions and auditory brain stem responses in hearing-impaired Saudi diabetic patients

Objective: To compare otoacoustic emissions and auditory brain stem responses in hearing-impaired diabetic patients and matched controls in order to determine the lesion site for hearing loss in diabetic patients.Subjects and Methods: This matched case-control study compared 88 hearing-impaired type 2 diabetic patients with 63 age- and gender-matched controls. Cochlear function was evaluated on the basis of otoacoustic emissions. The presence and amplitude of spontaneous otoacoustic emissions, distortion product amplitudes and latencies were recorded. Retrocochlear function was evaluated on the basis of auditory brainstem response. Absolute latencies of waves I, III, and V and inter-peak latencies of I–III, III–V, and I–V of the auditory brainstem were compared.Results: In the case of diabetic patients, no spontaneous otoacoustic emissions were produced, suggesting cochlear damage. Distortion product otoacoustic emission amplitudes at 1, 2, 4, and 6 kHz, but not the latencies, were significantly different between diabetic and control patients. Wave V latency was also significantly different between the 2 groups while the values of all other auditory brainstem parameters were similar.Conclusion: Cochlear damage may be one of the causes of hearing loss in diabetic patients. Distortion product otoacoustic emission amplitude may be used for assessment of hearing loss in diabetic patients.

Distortion product otoacoustic emissions: comparison of sequential vs. simultaneous presentation of primary tones

Distortion product otoacoustic emissions are one form of evoked otoacoustic emissions. DPOAEs provide the frequency specific information about the hearing status in mid and high frequency regions. But in most screening protocols TEOAEs are preferred as it requires less time compared to DPOAE. This is because, in DPOAE each stimulus is presented one after the other and responses are analyzed. Grason and Stadler Incorporation 60 (GSI-60) offer simultaneous presentation of four sets of primary tones at a time and checks for the DPOAE. In this mode of presentation, all the pairs are presented at a time and following that response is extracted separately whereas, in sequential mode primaries are presented in orderly fashion one after the other. In this article simultaneous and sequential protocols were used to compare the Distortion product otoacoustic emission amplitude, noise floor and administration time in individuals with normal hearing and mild sensori-neural (SN) hearing loss. In simultaneous protocols four sets of primary tones (i.e. 8 tones) were presented together whereas, in sequential presentation mode one set of primary tones was presented each time. Simultaneous protocol was completed in less than half the time required for the completion of sequential protocol. Two techniques yielded similar results at frequencies above 1000 Hz only in normal hearing group. In SN hearing loss group simultaneous presentation yielded signifi cantly higher noise floors and distortion product amplitudes. This result challenges the use of simultaneous presentation technique in neonatal hearing screening programmes and on other pathologies. This discrepancy between two protocols may be due to some changes in biomechanical process in the cochlear and/or due to higher distortion/noise produced by the system during the simultaneous presentation mode.

Long-term administration of salicylate enhances prestin expression in rat cochlea

Salicylate, a common drug frequently used long term in the clinic, is well known for causing reversible hearing loss and tinnitus. Our previous study, however, demonstrated that chronic administration of salicylate progressively raised the amplitude of distortion product of otoacoustic emissions (DPOAEs), which are mainly caused by (outer hair cell) OHC electromotility. How salicylate affects OHC electromotility to cause this paradoxical increase remains unclear. One possibility is that it could affect prestin, which is a motor protein that contributes to the mechano-electrical properties of OHCs. In this experiment, we assessed the effect of acute and chronic salicylate treatment on prestin expression. Interestingly, after long-term salicylate injection (200 mg/kg, twice daily for 14 days), prestin gene and protein levels were up-regulated about twofold. These levels returned to baseline 14 days after treatment stopped. Acute injection of salicylate (single injection, 400 mg/kg) did not affect prestin levels. These data reveal that chronic salicylate administration markedly, but reversibly, increased prestin levels which may contribute to the enhanced DPOAE amplitudes we observed previously with similar salicylate treatment, which may be responsible for salicylate-induced tinnitus generation.

Tuning of the Outer Hair Cell Motor by Membrane Cholesterol

Cholesterol affects diverse biological processes, in many cases by modulating the function of integral membrane proteins. We observed that alterations of cochlear cholesterol modulate hearing in mice. Mammalian hearing is powered by outer hair cell (OHC) electromotility, a membrane-based motor mechanism that resides in the OHC lateral wall. We show that membrane cholesterol decreases during maturation of OHCs. To study the effects of cholesterol on hearing at the molecular level, we altered cholesterol levels in the OHC wall, which contains the membrane protein prestin. We show a dynamic and reversible relationship between membrane cholesterol levels and voltage dependence of prestin-associated charge movement in both OHCs and prestin-transfected HEK 293 cells. Cholesterol levels also modulate the distribution of prestin within plasma membrane microdomains and affect prestin self-association in HEK 293 cells. These findings indicate that alterations in membrane cholesterol affect prestin function and functionally tune the outer hair cell.

Attention Effects on Distortion-Product Otoacoustic Emissions with Contralateral Speech Stimuli

This study investigated the effect of selective attention on the distortion-product otoacoustic emission (DPOAE) level through the use of environmentally meaningful, contralateral auditory stimuli. Four different conditions were used for measurement: quiet, contralateral noise, contralateral speech (unattended), and contralateral speech (attended). A statistically significant suppression effect for both the noise and speech conditions was found. However, there was no support for an auditory selective attention effect on the distortion-product amplitude.

The generation of psychoacoustic combination tones in relation to two-tone suppression effects in a computational model

The amplitude of the psychoacoustic distortion product 2 f1−f2 elicited by primaries f1 and f2 depends on the method of measurement. The cancellation-tone procedure gives consistently higher estimates of the distortion product than nonsimultaneous procedures. It was suggested that the difference could be attributed to suppression effects by the lower primary f1 [Smoorenburg, J. Acoust. Soc. Am. 52, 615–632 (1972)]. Simulations carried out with a computational model of the auditory periphery including a single, but distributed, compressive nonlinearity confirm the hypothesis; the amount of suppression produced at 2 f1−f2 by f1 equals the difference between simultaneous and nonsimultaneous methods of measuring the amplitude of the distortion product. This is in agreement with psychoacoustical data [Shannon and Houtgast, J. Acoust. Soc. Am. 68, 825–829 (1980)]. The model also reveals the importance of suppression effects by f1 to bring the phase of the traveling wave associated with the cancellation tone 2 f1−f2 in exact opposition with that of the distortion product 2 f1−f2 generated by the primaries. There is also evidence of suppression effects by the higher primary f2 when L2≫L1. In the model, cancellation occurs over a substantial portion of the basilar membrane near the characteristic place for 2 f1−f2.

Morphological and functional preservation of the outer hair cells from noise trauma by sound conditioning

Guinea pigs were sound conditioned to a low-level, long-term pure tone stimulus (1 kHz, 81 dB SPL, 24 days) before exposure to a traumatic noise (1 kHz, 105 dB SPL, 72 h). Auditory brainstem response thresholds and distortion product otoacoustic emissions were obtained at selected frequencies before sound conditioning and at day 1, 5, 10, and 15 during sound conditioning as well as on the final 24th day. Auditory brainstem responses at 1 and 2 kHz were not affected at any time during sound conditioning. The amplitude of the distortion product otoacoustic emission showed minor alterations (below 10 dB) at selected frequencies only during the initial stages (day 1, 5, and 10) of sound conditioning in some, but not all the animals. Distortion product amplitudes were similar to control values on the 15th and 24th day of conditioning. Surface preparations of the organ of Corti did not reveal any significant hair cell loss induced by sound conditioning. The effect of a traumatic exposure (1 kHz, 105 dB SPL, 72 h) on a control group and a sound conditioned group was determined. The distortion product otoacoustic emission amplitude measure 4 weeks after the cessation of the traumatic exposure revealed significant differences. The amplitude of the distortion product otoacoustic emission for the control group was depressed at all tested frequencies and at lower frequencies (2.8, 2.1, and 1.75 kHz) the emissions did not show an increase in response to increases in intensity. of the primaries. The sound conditioned group showed increases in distortion product amplitude with increases in the intensity of the primaries for all tested frequencies and statistically significant reductions from the pre-exposure values were not found. Surface preparations from the control group indicate that the traumatic noise exposure affected nearly 100% of the outer hair cells around the 14 mm distance from the round window. The sound conditioned group showed a significantly less (50%) outer hair cell loss than the control group. The sound conditioned group illustrated an altered pattern of damage after subsequent noise trauma. There were two distinct regions of outer hair cell loss, one being around the 16 mm distance and the other around the 12 mm distance from the round window. These results imply that the intrinsic properties of the outer hair cells and/or the organ of Corti have been altered by sound conditioning.

Coherence of frequency modulation is encoded by cochlear-generated distortion

Nonlinearities of the peripheral auditory system generate distortion products which present to the central auditory system as apparent acoustic stimuli. The frequency and amplitude of distortion products reflect the frequency, phase and amplitude relationship of the components of a complex stimulus. When the stimulus consists of harmonically-related primaries, the amplitudes of the major distortion products are a function of the relative phase of the presented (primary) tones. We have previously shown (McAnally and Calford, 1990) that the variation of amplitude of the distortion as a function of the relative phase of a pair of harmonically-related primaries is well modelled as a function of the interaction of the multiple modes of distortion which fall at the same frequency (e.g. difference frequency and cubic difference frequency). A possibility raised by this result is that coherence of frequency modulation (that which maintains harmonicity) could be encoded in the amplitude of distortion. This was examined in measurements of both the cochlear microphonic potential (CM) and the responses of auditory nerve fibers in anaesthetized cats. Very small deviations from coherence of frequency modulation produced changes in the amplitude of the CM potential at the frequency of distortion. Also the discharges of auditory nerve fibres tuned to the frequency of distortion were found to be modulated at the same frequency as the amplitude changes observed in the CM. There was no variation in distortion amplitude in the CM and no modulation of auditory nerve discharges when primaries were frequency modulated coherently. It is suggested that amplitude modulation of distortion gives the auditory system its demonstrated sensitivity to minor departures from coherence of frequency-modulated, harmonically-related tones.

Effects of altering organ of Corti on cochlear distortion products f2 - f1 and 2f1 - f2.

1. Single cochlear nerve fiber recordings from unexposed chinchillas show spatial distributions of amplitude and phase of the distortion products f2 - f1 and 2f1 - f2 similar to those previously reported for the cat (35, 37, 42). 2. Damaging the organ of Corti in the region corresponding to the frequencies of a two-tone stimulus substantially reduces the amplitude of these distortion products at their characteristic places. 3. The distortion products 2f - f1 and 2f1 - f2 thus appear to be generated in the organ of Corti in the region of the primary-frequency places. 4. The neural responses suggest that the distortion products are propagated in the motion of the cochlear partition like externally applied stimulus tones at the distortion frequencies wih a similar spatial distribution of distortion product amplitude and phase. Models of the cochlea that assume nonlinear cochlear-partition dynamics can account for the similarity by demonstrating that distortion products generated by cochlear-partition nonlinearity can propagate apicalward in the motion of the cochlear partition. 5. Models of the cochlea using a linear-system model for cochlear partition motion, in cascade with a nonlinear transduction stage and a subsequent sharp filter, are inadequate to account for present observations, unless two currently implausible assumptions are made: a) stimulus tones near 4 kHz must propagate in normal cochleas at least as far apically as the 300-Hz place with sufficient amplitude to generate f2 - f1 there, and b) damage to the organ of Corti must interfere with this propagation of 4-kHz stimulus tones to the 300-Hz place. 6. Distortion generation in the cochlea is sensitive to delicate alterations of the organ of Corti. Short moderate-intensity exposures to sound can reversibly reduce the amplitudes of the distortion products f2 - f1 and 2f1 - f2 seen in responses from cochlear nerve fibers with characteristic frequencies (CF) near the distortion frequencies. Since such exposures do ot produce permanent structural changes visible under light microscopy, it seems most reasonable to believe that subtle changes in the organ of Corti (most likely in the hair cells themselves) in the region most responsive to f1 and f2 reduce the generation of mechanically present distortion products.