Auditory evoked potentials: Differences by sex, race, and menstrual cycle and correlations with common psychoacoustical tasks.

Auditory brainstem responses (ABRs) and auditory middle-latency responses (AMLRs) to a click stimulus were measured in about 100 subjects. Of interest were the sex differences in those auditory evoked potentials (AEPs), the correlations between the various AEP measures, and the correlations between the AEP measures and measures of otoacoustic emissions (OAEs) and behavioral performance also measured on the same subjects. Also of interest was how the menstrual cycle affected the various AEP measures. Most ABR measures and several AMLR measures exhibited sex differences, and many of the former were substantial. The sex differences tended to be larger for latency than for amplitude of the waves, and they tended to be larger for a weak click stimulus than for a strong click. The largest sex difference was for Wave-V latency (effect size ~1.2). When subjects were dichotomized into Non-Whites and Whites, the race differences in AEPs were small within sex. However, sex and race interacted so that the sex differences often were larger for the White subjects than for the Non-White subjects, particularly for the latency measures. Contrary to the literature, no AEP measures differed markedly across the menstrual cycle. Correlations between various AEP measures, and between AEP and OAE measures, were small and showed no consistent patterns across sex or race categories. Performance on seven common psychoacoustical tasks was only weakly correlated with individual AEP measures (just as was true for the OAEs also measured on these subjects). AMLR Wave Pa unexpectedly did not show the decrease in latency and increase in amplitude typically observed for AEPs when click level was varied from 40 to 70 dB nHL (normal Hearing Level). For the majority of the measures, the variability of the distribution of scores was greater for the males than for the females.

Correlations between otoacoustic emissions and performance in common psychoacoustical tasks.

Performance was measured on seven common psychoacoustical tasks for about 75 highly trained subjects. Because some psychoacoustical outcomes varied by race, the subjects were partitioned into White and Non-White categories for analysis. Sex, race, and menstrual-cycle differences in performance are described in a companion paper [McFadden, Pasanen, Maloney, Leshikar, and Pho (2018). J. Acoust. Soc. Am. 143, 2338-2354]. Also measured for all subjects were three types of otoacoustic emissions (OAEs): spontaneous otoacoustic emissions (SOAEs), click-evoked otoacoustic emissions (CEOAEs), and distortion-product otoacoustic emissions (DPOAEs). The experimental question was whether and how OAEs were correlated with psychoacoustical performance. In accord with past findings, the SOAEs and CEOAEs exhibited substantial sex and race differences, but the DPOAEs did not. Somewhat surprisingly, the correlations between OAEs and psychoacoustical performance were generally weak. No form of OAE was highly correlated with any psychoacoustical task for both sexes within a race category. Thus, there was no compelling evidence that the mechanisms underlying OAEs also contribute systematically to performance in any of the simultaneous or temporal masking tasks studied here. Especially surprising were the weak correlations between OAEs and detection of a tone in the quiet. Apparently individual differences in psychoacoustical performance reside more in post-cochlear (neural) mechanisms than in individual differences in the cochlear ("mechanical") mechanisms underlying the OAEs measured here.

Differences in common psychoacoustical tasks by sex, menstrual cycle, and race.

The psychoacoustical literature contains multiple reports about small differences in performance depending upon the sex and phase of the menstrual cycle of the subjects. In an attempt to verify these past reports, a large-scale study was implemented. After extensive training, the performance of about 75 listeners was measured on seven common psychoacoustical tasks. For most tasks, the signal was a 3.0-kHz tone. The initial data analyses failed to confirm some past outcomes. Additional analyses, incorporating the limited information available about the racial background of the listeners, did confirm some of the past reports, with the direction and magnitude of the differences often diverging for the White and Non-White listeners. Sex differences and race differences interacted for six of the seven tasks studied. These interactions suggest that racial background needs to be considered when making generalizations about human auditory performance, and when considering failures of reproducibility across studies. Menstrual differences were small, but generally larger for Whites than Non-Whites. Hormonal effects may be responsible for the sex and cycle differences that do exist, and differences in intra-cochlear melanocytes may account for the race differences.

Changes in otoacoustic emissions during selective auditory and visual attention.

Previous studies have demonstrated that the otoacoustic emissions (OAEs) measured during behavioral tasks can have different magnitudes when subjects are attending selectively or not attending. The implication is that the cognitive and perceptual demands of a task can affect the first neural stage of auditory processing-the sensory receptors themselves. However, the directions of the reported attentional effects have been inconsistent, the magnitudes of the observed differences typically have been small, and comparisons across studies have been made difficult by significant procedural differences. In this study, a nonlinear version of the stimulus-frequency OAE (SFOAE), called the nSFOAE, was used to measure cochlear responses from human subjects while they simultaneously performed behavioral tasks requiring selective auditory attention (dichotic or diotic listening), selective visual attention, or relative inattention. Within subjects, the differences in nSFOAE magnitude between inattention and attention conditions were about 2-3 dB for both auditory and visual modalities, and the effect sizes for the differences typically were large for both nSFOAE magnitude and phase. These results reveal that the cochlear efferent reflex is differentially active during selective attention and inattention, for both auditory and visual tasks, although they do not reveal how attention is improved when efferent activity is greater.

Otoacoustic emissions, auditory evoked potentials and self-reported gender in people affected by disorders of sex development (DSD).

Both otoacoustic emissions (OAEs) and auditory evoked potentials (AEPs) are sexually dimorphic, and both are believed to be influenced by prenatal androgen exposure. OAEs and AEPs were collected from people affected by 1 of 3 categories of disorders of sex development (DSD) - (1) women with complete androgen insensitivity syndrome (CAIS); (2) women with congenital adrenal hyperplasia (CAH); and (3) individuals with 46,XY DSD including prenatal androgen exposure who developed a male gender despite initial rearing as females (men with DSD). Gender identity (GI) and role (GR) were measured both retrospectively and at the time of study participation, using standardized questionnaires. The main objective of this study was to determine if patterns of OAEs and AEPs correlate with gender in people affected by DSD and in controls. A second objective was to assess if OAE and AEP patterns differed according to degrees of prenatal androgen exposure across groups. Control males, men with DSD, and women with CAH produced fewer spontaneous OAEs (SOAEs) - the male-typical pattern - than control females and women with CAIS. Additionally, the number of SOAEs produced correlated with gender development across all groups tested. Although some sex differences in AEPs were observed between control males and females, AEP measures did not correlate with gender development, nor did they vary according to degrees of prenatal androgen exposure, among people with DSD. Thus, OAEs, but not AEPs, may prove useful as bioassays for assessing early brain exposure to androgens and predicting gender development in people with DSD.

Selective attention reduces physiological noise in the external ear canals of humans. I: auditory attention.

In this study, a nonlinear version of the stimulus-frequency OAE (SFOAE), called the nSFOAE, was used to measure cochlear responses from human subjects while they simultaneously performed behavioral tasks requiring, or not requiring, selective auditory attention. Appended to each stimulus presentation, and included in the calculation of each nSFOAE response, was a 30-ms silent period that was used to estimate the level of the inherent physiological noise in the ear canals of our subjects during each behavioral condition. Physiological-noise magnitudes were higher (noisier) for all subjects in the inattention task, and lower (quieter) in the selective auditory-attention tasks. These noise measures initially were made at the frequency of our nSFOAE probe tone (4.0 kHz), but the same attention effects also were observed across a wide range of frequencies. We attribute the observed differences in physiological-noise magnitudes between the inattention and attention conditions to different levels of efferent activation associated with the differing attentional demands of the behavioral tasks. One hypothesis is that when the attentional demand is relatively great, efferent activation is relatively high, and a decrease in the gain of the cochlear amplifier leads to lower-amplitude cochlear activity, and thus a smaller measure of noise from the ear.

Selective attention reduces physiological noise in the external ear canals of humans. II: visual attention.

Human subjects performed in several behavioral conditions requiring, or not requiring, selective attention to visual stimuli. Specifically, the attentional task was to recognize strings of digits that had been presented visually. A nonlinear version of the stimulus-frequency otoacoustic emission (SFOAE), called the nSFOAE, was collected during the visual presentation of the digits. The segment of the physiological response discussed here occurred during brief silent periods immediately following the SFOAE-evoking stimuli. For all subjects tested, the physiological-noise magnitudes were substantially weaker (less noisy) during the tasks requiring the most visual attention. Effect sizes for the differences were >2.0. Our interpretation is that cortico-olivo influences adjusted the magnitude of efferent activation during the SFOAE-evoking stimulation depending upon the attention task in effect, and then that magnitude of efferent activation persisted throughout the silent period where it also modulated the physiological noise present. Because the results were highly similar to those obtained when the behavioral conditions involved auditory attention, similar mechanisms appear to operate both across modalities and within modalities. Supplementary measurements revealed that the efferent activation was spectrally global, as it was for auditory attention.

Comparing behavioral and physiological measures of combination tones: sex and race differences.

Both distortion-product otoacoustic emissions (DPOAEs) and performance in an auditory-masking task involving combination tones were measured in the same frequency region in the same ears. In the behavioral task, a signal of 3.6 kHz (duration 300 ms, rise/fall time 20 ms) was masked by a 3.0-kHz tone (62 dB SPL, continuously presented). These two frequencies can produce a combination tone at 2.4 kHz. When a narrowband noise (2.0-2.8 kHz, 17 dB spectrum level) was added as a second masker, detection of the 3.6-kHz signal worsened by 6-9 dB (the Greenwood effect), revealing that listeners had been using the combination tone at 2.4 kHz as a cue for detection at 3.6 kHz. Several outcomes differed markedly by sex and racial background. The Greenwood effect was substantially larger in females than in males, but only for the White group. When the magnitude of the Greenwood effect was compared with the magnitude of the DPOAE measured in the 2.4 kHz region, the correlations typically were modest, but were high for Non-White males. For many subjects, then, most of the DPOAE measured in the ear canal apparently is not related to the combination-tone cue that is masked by the narrowband noise.

Relationships between otoacoustic emissions and a proxy measure of cochlear length derived from the auditory brainstem response.

Brief tones of 1.0 and 8.0 kHz were used to evoke auditory brainstem responses (ABRs), and the differences between the wave-V latencies for those two frequencies were used as a proxy for cochlear length. The tone bursts (8 ms in duration including 2-ms rise/fall times, and 82 dB in level) were, or were not, accompanied by a continuous, moderately intense noise band, highpass filtered immediately above the tone. The proxy values for length were compared with various measures of otoacoustic emissions (OAEs) obtained from the same ears. All the correlations were low, suggesting that cochlear length, as measured by this proxy at least, is not strongly related to the various group and individual differences that exist in OAEs. Female latencies did not differ across the menstrual cycle, and the proxy length measure exhibited no sex difference (either for menses females vs. males or midluteal females vs. males) when the highpass noises were used. However, when the subjects were partitioned into Whites and Non-Whites, a substantial sex difference in cochlear length did emerge for the White group, although the correlations with OAEs remained low. Head size was not highly correlated with any of the ABR measures.

Overshoot using very short signal delays.

The detectability of a 10-ms tone masked by a 400-ms wideband noise was measured as a function of the delay in the onset of the tone compared to the onset of the noise burst. Unlike most studies like this on auditory overshoot, special attention was given to signal delays between 0 and 45 ms. Nine well-practiced subjects were tested using an adaptive psychophysical procedure in which the level of the masking noise was adjusted to estimate 79% correct detections. Tones of both 3.0 and 4.0 kHz, at different levels, were used as signals. For the subjects showing overshoot, detectability remained approximately constant for at least 20-30 ms of signal delay, and then detectability began to improve gradually toward its maximum at about 150-200 ms. That is, there was a "hesitation" prior to detectability beginning to improve, and the duration of this hesitation was similar to that seen in physiological measurements of the medial olivocochlear (MOC) system. This result provides further support for the hypothesis that the MOC efferent system makes a major contribution to overshoot in simultaneous masking.

Overshoot measured physiologically and psychophysically in the same human ears.

A nonlinear version of the stimulus-frequency otoacoustic emission (SFOAE) was measured using stimulus waveforms similar to those used for behavioral overshoot. Behaviorally, the seven listeners were as much as 11 dB worse at detecting a brief tonal signal (4.0 kHz, 10 ms in duration) when it occurred soon after the onset of a wideband masking noise (0.1-6.0 kHz; 400 ms in duration) than when it was delayed by about 200 ms, and the nonlinear SFOAE measure exhibited a similar effect. When either lowpass (0.1-3.8 kHz) or bandpass noise (3.8-4.2 kHz) was used instead of the wideband noise, the physiological and behavioral measures again were similar. When a highpass noise (4.2-6.0 kHz) was used, the physiological and behavioral measures both showed no overshoot-like effect for five of the subjects. The physiological response to the tone decayed slowly after the termination of the noise, much like the time course of resetting for behavioral overshoot. One subject exhibited no overshoot behaviorally even though his cochlear responses were like those of the other subjects. Overall, the evidence suggests that some basic characteristics of overshoot are obligatory consequences of cochlear function, as modulated by the olivocochlear efferent system.

Properties of a nonlinear version of the stimulus-frequency otoacoustic emission.

A procedure for extracting the nonlinear component of the stimulus-frequency otoacoustic emission (SFOAE) is described. This nSFOAE measures the amount by which the cochlear response deviates from linear additivity when the input stimulus is doubled in amplitude. When a 4.0-kHz tone was presented alone, the magnitude of the nSFOAE response remained essentially constant throughout the 400-ms duration of the tone; response magnitude did increase monotonically with increasing tone level. When a wideband noise was presented alone, nSFOAE magnitude increased over the initial 100- to 200-ms portion of the 400-ms duration of the noise. When the tone and the wideband noise were presented simultaneously, nSFOAE magnitude decreased momentarily, then increased substantially for about the first 100 ms and then remained strong for the remainder of the presentation. Manipulations of the noise bandwidth revealed that the low-frequency components were primarily responsible for this rising, dynamic response; no rising segment was seen with bandpass or highpass noise. The rising, dynamic nSFOAE response is likely attributable to activation of the medial olivocochlear efferent system. This perstimulatory emission appears to have the potential to provide information about the earliest stages of auditory processing for stimuli commonly used in psychoacoustical tasks.

Effect of prenatal androgens on click-evoked otoacoustic emissions in male and female sheep (Ovis aries).

Otoacoustic emissions (OAEs) were measured in male and female Suffolk sheep (Ovis aries). Some sheep had been administered androgens or estrogens during prenatal development, some were gonadectomized after birth, and some were allowed to develop normally. As previously reported for spotted hyenas, gonadectomy did not alter the OAEs for either sex; accordingly, the untreated/intact and the untreated/gonadectomized animals were pooled to form the control groups. The click-evoked otoacoustic emissions (CEOAEs) exhibited by the female control group (N=12) were slightly stronger (effect size=0.42) than those in the male control group (N=15), which is the same direction of effect reported for humans and rhesus monkeys. Females administered testosterone prenatally (N=16) had substantially weaker (masculinized) CEOAEs than control females (effect size=1.15). Both of these outcomes are in accord with the idea that prenatal exposure to androgens weakens the cochlear mechanisms that underlie the production of OAEs. The CEOAEs of males administered testosterone prenatally (N=5) were not different from those of control males, an outcome also seen in similarly treated rhesus monkeys. Males administered dihydrotestosterone (DHT) prenatally (N=3) had slightly stronger (hypo-masculinized) CEOAEs than control males. No spontaneous otoacoustic emissions (SOAEs) were found in any ears, a common finding in non-human species. To our knowledge, this is the first ruminant species measured for OAEs.

Dissociation between distortion-product and click-evoked otoacoustic emissions in sheep (Ovis aries).

Distortion-product otoacoustic emissions (DPOAEs) were weak or absent in about one-third of sheep (Ovis aries) of both sexes tested for otoacoustic emissions (OAEs) even though their click-evoked OAEs (CEOAEs) seemingly were typical of other sheep of the same sex. Various pieces of evidence suggest that the absence of measurable DPOAEs was unlikely to be attributable to anesthetic effects, a poorly located probe tip, a pressure differential between middle and outer ears, season of the year, body position during testing, temperature effects, or previous medical history. Sheep apparently can exhibit a marked dissociation between DPOAEs and CEOAEs. In those sheep having measurable DPOAEs, the DPOAEs were stronger in males than in females, which is the opposite direction of effect from the CEOAEs measured in these same sheep and in humans. In female sheep exposed to higher-than-normal levels of androgens during gestation, the measurable DPOAEs were stronger than in untreated females. Although this also was the opposite direction of effect from expected, it still was a shift in the male direction, in accord with past findings about the masculinizing effects of androgens on OAEs. In sheep, androgen exposure appears to have different effects on the mechanisms underlying DPOAEs from those underlying CEOAEs.

Masculinized otoacoustic emissions in female spotted hyenas (Crocuta crocuta).

In humans and rhesus monkeys, click-evoked otoacoustic emissions (CEOAEs) are stronger in females than in males, and there is considerable circumstantial evidence that this sex difference is attributable to the greater exposure to androgens prenatally in males. Because female spotted hyenas are highly androgenized beginning early in prenatal development, we expected an absence of sexual dimorphism in the CEOAEs of this species. The CEOAEs obtained from 9 male and 7 female spotted hyenas confirmed that expectation. The implication is that the marked androgenization to which female spotted hyenas are exposed masculinizes the cochlear mechanism responsible for CEOAEs. The CEOAEs measured in 3 male and 3 female hyenas that had been treated with anti-androgenic agents during prenatal development were stronger than the CEOAEs of the untreated animals, in accord with the implied inverse relationship between prenatal androgen exposure and the strength of the cochlear mechanisms producing CEOAEs. The CEOAEs of three ovariectomized females and two castrated males were essentially the same as those for the untreated females and males, suggesting that there is little or no activational effect of hormones on CEOAE strength in spotted hyenas. Distortion product OAEs (DPOAEs) also were measured. Those sex differences also were generally small (as they are in humans), and the effects of the anti-androgen agents were inconsistent. Thus, prenatal androgen exposure apparently does affect OAEs, but the effects appear to be greater for the reflection-based cochlear mechanism that underlies CEOAEs than for the nonlinear cochlear mechanism underlying DPOAEs.

Sex differences in otoacoustic emissions measured in rhesus monkeys (Macaca mulatta).

Click-evoked otoacoustic emissions (CEOAEs) and distortion-product OAEs (DPOAEs) were measured in about 60 rhesus monkeys. CEOAE strength was substantially greater in females than in males, just as in humans. DPOAE strength was generally slightly stronger in females, just as in humans. In males, CEOAEs were weaker (more masculine) in the fall breeding season and in winter than in the summer. In females, CEOAEs were slightly stronger (more feminine) in the fall, when sex steroids are elevated in females (and males), than in the summer when rhesus monkeys are reproductively quiescent. Thus, the sex differences in CEOAEs were greater in the fall than in the summer. We presume that the seasonal fluctuations in OAEs reflect activational hormonal effects, while the basic sex differences in OAEs likely reflect organizational effects of prenatal androgen exposure. Some monkeys of both sexes had been treated with additional testosterone or the anti-androgen flutamide during prenatal development. In accord with expectations, prenatal androgen treatment weakened CEOAEs in females, and prenatal flutamide treatment strengthened CEOAEs in males. For DPOAEs, the differences between treated and untreated groups were mostly small and often inconsistent. Taken as a whole, the data from both rhesus monkeys and humans suggest that the linear, reflection-based mechanism of OAE production that underlies CEOAEs is more sensitive to prenatal androgenic processes than is the nonlinear distortion mechanism that underlies DPOAEs.