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To study the functional development of the medial olivocochlear system, transient-evoked otoacoustic emission suppression experiments were conducted in 73 ears of 38 pre-term and 11 full-term neonates. The continuous contralateral stimulation was a broad band white noise, presented at 70 dB SPL. Efferent suppression was determined by subtracting the without-contralateral stimulation condition from the with-contralateral stimulation condition. Across this population, a mean suppression effect of contralateral stimulation on transient-evoked otoacoustic emissions was found, with most of the suppression effect observed after 8 ms. The amount of suppression is linearly, positively correlated with the conceptional age. In the subgroup of bilaterally tested neonates, the suppression of transient-evoked otoacoustic emissions is similar in the right ear and the left ear in subjects whose conceptional age is less than 36 weeks and significantly higher in the right ear than in the left ear in older neonates. This last observation was seen at frequencies where transient-evoked otoacoustic emission amplitudes became higher in the right ear than in the left ear as the conceptional age increased, a finding already reported in adults. This study shows that the functional adult pattern of the medial efferent system, probably involved in the detection of signals in noise such as speech sounds, seems to appear gradually in neonates and represents one of the several arguments in favor of functional auditory lateralization in humans, with a right ear advantage.

The f2/f1 frequency ratio of 1.3 in combination with stimulus levels of L1/L2 = 50/60 and 50/50 dB SPL produced a higher level of distortion product otoacoustic emissions (DPOAE) in the heterozygous (+/dn) mice than in the homozygous (+/+) mice. These results suggest that the dn gene carriers have a unique cochlear trait which may be related to the dn gene locus and expressed via a frequency- and intensity-dependent DPOAE function.

Transient evoked otoacoustic emissions (TEOAEs) were recorded to clicks presented at peak sound pressures of 50, 55, 60, 65 and 70 dB while continuous contralateral white noise was varied from 10 dB below to 10 dB above the click level. Suppression increased predictably with suppressor noise level for any given click level. However, when the suppressor noise level was held constant, suppression was greater for lower click levels. This observation is consistent with the association of suppression of otoacoustic emissions with active cochlear processes and efferent function at low intensity levels.

Distortion product otoacoustic emissions (DPOE) were obtained from five different hearing mouse groups: CBA/J, MOLF/Rk, ct (homozygous normal mice of the curly-tail stock), and the F1 hybrid offspring of the matings CBA/J x dn/dn and MOLF/Rk x dn/dn (dn/dn mice are the curly-tail stock with recessive deafness). The DPOE patterns of the CBA/J and ct strains were similar to each other and different from that of the MOLF/Rk. The two sets of F1 hybrid mice, (CBA/J x dn/dn)F1 and (MOLF/Rk x dn/dn)F1, were found to have significantly larger DPOE amplitudes than their hearing parent strains, MOLF/Rk and CBA/J, respectively. In addition, the DPOE amplitudes were greater for the offspring of the MOLF/Rk x dn/dn cross than for those of the CBA/J x dn/dn cross, even though they were lower for MOLF/Rk than for CBA/J. The distinct features of DPOE patterns among these five groups suggest that DPOE testing can be used for auditory phenotyping.

Maturation of the cochlea and afferent auditory units is reflected by changes in VIIIth nerve compound action potential (CAP) parameters. We studied auditory nerve CAPs evoked by low-intensity stimuli in Mongolian gerbils (Meriones unguiculatus) ranging in age from 22 to 92 days after birth. The gerbil CAP development is characterized by marked changes in latency, threshold, and amplitude during the first few weeks of life. CAP latency and CAP threshold reach adult-like values at about 1 month of age. In contrast, the CAP amplitude continues to grow in size even after 2 months. This dichotomy suggests that the development of afferent auditory nerve function in the gerbil is preceded by maturation of the mechanical processes of the middle ear and cochlea.

Accurate phenotyping of offspring from backcross matings between F1 heterozygous sound-responsive and deafness mice is an important step for the identification of the deafness (dn) gene (Keats et al., 1995). Here, we report the results of auditory phenotyping of backcross offspring who are either sound-responsive or deaf by recording the Preyer reflex elicited by hand clap, auditory brainstem responses (ABRs), and 2f1-f2 distortion product otoacoustic emissions (DPOEs). Our results show that the Preyer reflex observation alone is inadequate for auditory phenotyping; a more precise test such as a click-evoked ABR recording is needed for auditory phenotyping. DPOE recording results in identification of sound-responsive or deaf mice as accurately as the click-evoked ABR testing. In addition, because the DPOE amplitude function is in good agreement with the ABR threshold in frequency sensitivity and specificity for stimulus frequencies between 1 and 16 kHz, the DPOE recording can be considered as an alternate test for auditory phenotyping.

We studied the efferent suppression of click-evoked otoacoustic emissions with 65 dB SPL of white noise presented to left, right, or sometimes both, ears for 408 ms. Each burst of noise preceded a series of four unipolar 80 microseconds 65 dB peak Sound Pressure clicks, presented to the left ear only. The first click of the four-click group followed the end of the noise by either 1, 2, 5, 10, 20, 50, 100 or 200 ms; each subsequent click was offset by 20 additional ms via an ILO88 system with special programming modifications. Conditions were alternated so that a 'without noise' condition preceded a 'with noise' condition for three repetitions of 600 clicks per trial. Seven subjects with normal hearing participated in the study, and three of the seven participated in a test-retest reliability study. Results showed the greatest suppression followed binaural stimulation ending within one to five ms of the first click in the pulse train. Somewhat less suppression was seen following ipsilateral stimulation. The least amount of suppression was seen following contralateral stimulation, suggesting that previous research using contralateral stimulation may underestimate efferent effects. We saw no effects when the end of the noise was 100 ms or more away from the beginning of the click train.

We studied whether same-frequency contralateral tones of 65 dB pSPL (peak Sound Pressure Level) suppress the VIIIth nerve compound action potential (CAP) evoked by 40-45 dB pSPL tone pips in the Mongolian gerbil from 22 to 92 days after birth (DAB). The primary stimuli were tone pips of 1, 2, 4, 8, and 10 kHz; only the 1 kHz CAP amplitude was suppressed significantly by tones of the same frequency. The suppression was seen at 22 DAB, and underwent little relative change with development.

Click-evoked otoacoustic emissions from nominal 80 dB pSP (peak sound pressure) 80-microseconds pulses presented at 50 pulses per second were collected from the right ears of eleven normal hearing subjects using an ILO88 Otodynamic Analyzer in the non-linear mode. Clicks, pure tones, and narrow bands of noise were then presented to their left ears through insert earphones. The 80-microseconds contralateral clicks ranged in intensity from 80 dB pSP in 5 dB steps down to 60 dB pSP but data on only 10 of the subjects were collected successfully. The pure tones and narrow bands of noise centered at 250, 500, 1000, 2000, and 4000 Hz were also presented through insert phones at 20, 40, 60 and 80 dB HL (Hearing Level) to all 11 subjects. The mean overall 'echo amplitude' without contralateral stimuli was 11 dB SPL and underwent more than 3 dB of overall suppression in response to the noises which were the most effective of the contralateral suppressors. When we analyzed the echo suppression to noise in 2-ms segments, we found consistent contralateral suppression of 3-4 dB concentrated in the time zones after 8 ms. Time shifts of more than 200 microseconds between the control and experimental traces were also observed in the same zones. The clicks were the next most effective suppressors, but showed their amplitude and time effects in somewhat earlier time zones. The tones were the least effective suppressors suggesting that efferent effects we measured in the human system are not strongly tonotopic. Because 'non-linear' mode high intensity clicks were deliberately selected as stimuli to evoke the TEOAE's, the emissions and their suppression can represent neither the 'true' TEOAE nor all of the efferent system's suppression abilities.

We present here two patients and three control subjects to demonstrate the clinical utility of studying evoked otoacoustic emissions and their contralateral suppression, as an aid to the delineation of afferent neuron dysfunction and possible lack of efferent suppression. The key patients here who fail to show contralateral suppression of their very robust otoacoustic emissions, concomitantly show paradoxically absent auditory brainstem responses (ABRs) and absence of middle ear muscle reflexes despite normal audiograms in the 2 kHz region and normal tympanograms. One of these patients has nearly normal pure tone sensitivity up to 3 kHz. The other has normal sensitivity in the 2 kHz region, but poor sensitivity on either side of that frequency. In addition, the two patients of interest show absent masking level differences and inordinately poor speech discrimination. Three 'foils' are presented: one patient with poor hearing on either side of 2 kHz, one with Bell's Palsy, and the third with bilateral temporal lobe disease. These patients show respectively that (1) isolated normal hearing at 2 kHz, (2) absence of middle ear muscle reflexes and (3) conscious cortical awareness of sound do not contribute directly to this intriguing clinical state. We propose that these patients with absent ABRs suffer from an auditory nervous system dysfunction which disrupts access to the efferent system. This condition also disables whatever systems contribute to the neural synchrony inherent in recording compound far-field action potentials such as the ABR. There are a number of hypotheses to be considered here. One suggests that the key patients are deficient in synchronous activation of Type I afferent fibers to the degree that they cannot activate efferent feedback, or they may be able to use only so-called Type II afferent neurons to support their normal zones of pure tone sensitivity. A less likely consideration focuses on the notion that discharge of primary neurons might be in some way synchronized by an efferent system which in these patients is the primary source of deficit.

A derived response method of acquiring frequency specific auditory evoked potentials that utilizes a pure tone in combination with a toneburst is applied to the measurement of hearing sensitivity in guinea pigs, chinchillas and pocket gophers. Two experiments which demonstrate that thresholds acquired via tone-derived responses are 10 to 15 dB more sensitive than thresholds to solitary tonebursts are described. The derived potentials approximate behaviorally acquired thresholds at frequencies of 0.5 kHz and above. This technique may provide a more rapid means of assessing hearing sensitivity in laboratory animals than by behavioral means.

A technique is described which verifies neural activity to a very faint continuous sine wave through subtraction of two different far-field whole nerve action potentials from one another. A brief transient is presented to an animal in order to elicit a supra-threshold action potential. The technique is then repeated, but on the second trial a near-threshold sine wave is mixed with the transient and another action potential is collected. The resultant evoked is then subtracted from the evoked potential generated by the transient alone and a small but persistent difference potential is acquired that presumably represents the unit activity occupied by the continuous sine wave. Four experiments are presented to show the validity of this technique, along with a surprising stability of the derived-response latency despite a 30 dB range of the probes. The technique may have promise in predicting behavioral responses to sinusoids acquired from individual animals.

Others have shown that in animals born with immature cochleae the basal turn undergoes changes in function during the early days of postnatal life. We examined whether similar changes could be detected in the guinea pig, an animal born with a functionally mature cochlea. Our results indicate that no changes occur in the function of the basal turn of the guinea pig cochlea immediately after birth.

Left-handed individuals show a 4 ms later Wave Pb in the 45-60 ms latency range of the auditory middle latency response (MLR) than right-handed individuals. Examination of auditory evoked potentials in fifteen right-handed and fifteen left-handed normal hearing adults showed that this difference was not evident in time periods earlier or later than 45-60 ms. The isolation of this latency difference to a specific time period suggests that the source or sources of Wave Pb may be an independent physiological index which correlates with hand preference.