Carolina Abdala

Auditory threshold sensitivity of the human neonate as measured by the auditory brainstem response

The absolute auditory sensitivity of the human newborn infant was investigated using auditory brainstem response thresholds (ABR). ABRs were elicited with clicks and tone-bursts of 0.5, 1.5, 4.0 and 8.0 kHz, embedded in notched noise, in healthy, full-term human neonates and young adults with known, normal-hearing sensitivity. Stimuli were calibrated using a probe microphone positioned near the tympanic membrane in the ear canal of each subject to control for differences in resonance characteristics of infant and adult ear canals. ABR thresholds were also characterized relative to group psychophysical thresholds (nHL) and relative to individual psychophysical threshold or sensation level (SL) for the adult subjects. Infant ABR thresholds measured in p.e. SPL for all stimuli are elevated by to 3-25 dB relative to adult thresholds. Threshold elevation is greatest for the high-frequency stimuli. Result are consistent with neural immaturity for high-frequency stimuli in the auditory system of human neonates.

Cochlear receptor (microphonic and summating potentials, otoacoustic emissions) and auditory pathway (auditory brain stem potentials) activity in auditory neuropathy.

Objective To define both auditory nerve and cochlear receptor functions in subjects with auditory neuropathy (AN). Design We tested 33 AN subjects (66 ears) and compared them with 21 healthy subjects (28 ears). In AN subjects, the average pure-tone (1, 2, and 4 kHz) threshold loss was 57 dB HL. Click stimuli were used to elicit transient evoked otoacoustic emissions (TEOAEs), cochlear microphonics (CMs), and auditory brain stem responses (ABRs). Both cochlear and ABR potentials were recorded from surface electrodes (vertex-ipsilateral mastoid) using averaging procedures. The amplitudes and latencies of CMs and ABRs and the amplitude of the TEOAEs were analyzed. Results CM amplitudes recorded from normal ears decreased as a function of subject age. CMs recorded from AN subjects fell within the normal age-adjusted range in 60% of the subjects and were >2 SEEs (standard error of estimate) above the age-adjusted normal regression in 40% of the subjects. TEOAEs were absent in 19 (30%) AN ears (bilaterally in eight, and unilaterally in three subjects) and were present in 44 ears. In AN subjects, correlations among CM amplitude, TEOAE amplitude, and pure-tone average thresholds were not significantly related. CM amplitudes were not significantly different whether TEOAEs or ABRs were present or absent. The ABR was present in 21% of AN subjects and consisted of a low-amplitude Wave V without a preceding Wave I. Measures of CM amplitude and PTA hearing loss were not significantly different in those AN ears with a preserved ABR compared with ears with absent ABRs. Summating potentials to transient click stimuli were of small amplitude (<0.1 &mgr;V) and detectable in approximately 50% of the AN and healthy control subjects limiting formal analysis of summating potentials. Conclusions In a significant proportion of AN subjects, we found abnormalities of cochlear receptor function, including elevated CM amplitudes and absence of TEOAEs. These two abnormalities occurred independently of each other. A low amplitude Wave V of the ABR was found in approximately one-fifth of AN subjects, evidence that neural synchrony can be partially preserved in some subjects with this disorder.

Distortion product otoacoustic emission (2 f1−f2) amplitude as a function of f2/f1 frequency ratio and primary tone level separation in human adults and neonates

Distortion product otoacoustic emission (DPOAE) (2f1-f2) amplitude is dependent upon both the frequency ratio and level separation of the eliciting primary tones. In adults it has been established that, on average, a f2/f1 ratio of 1.22 is optimal for evoking the most robust DPOAE; DPOAE amplitude is systematically reduced when f2/f1 ratio is either increased or decreased, thus forming a bandpass function (Harris et al., 1989). The frequency ratio function (DPOAE amplitude x f2/f1 ratio) is thought to reflect the filtering properties of the cochlea (Allen and Fahey, 1993; Brown et al., 1993). Primary tone level separation also influences DPOAE amplitude, with a 10- to 15-dB level difference between the primary tones (L1 > L2) typically generating largest amplitude in adults. Equivalent studies have not been conducted in neonates. The present study evoked the 2f1-f2 DPOAE in adults, term and premature neonates to define the optimal f2/f1 ratio and L1-L2 level separation and to investigate the filtering properties of the developing cochlea. Two f2 frequencies were investigated: 1500 and 6000 Hz. F2 was held constant while f1 was varied to produce 13 frequency ratios. Primary tone level separation varied from 15 to 0- in 5-dB intervals. ANOVA were conducted on the resulting f2/f1 frequency ratio and level separation data. Results showed that the mean optimal frequency ratio for DPOAE generation is comparable in adults and neonates. Also, either a 15- or 10-dB level separation (L1 > L2) produced the largest DPOAE amplitude for adults and term neonates whereas DPOAEs from premature neonates appeared to be relatively insensitive to primary tone level separation. The f2/f1 frequency ratio functions were similar in shape, slope, and bandwidth for adults and neonates, suggesting adult-like cochlear filtering prior to term birth. This finding is in agreement with previous work from our laboratory reporting adult-like DPOAE suppression tuning curves in term-born neonates [Abdala et al., Hear. Res. (1996)].

Distortion product otoacoustic emission suppression tuning curves in human adults and neonates

Distortion product otoacoustic emission (DPOAE) iso-suppression tuning curves (STC) were generated in 15 normal-hearing adults and 16 healthy term-born neonates for three f2 frequencies. The 2f1-f2 DPOAE was elicited using f2/f1 = 1.2, LI = 1.2, LI = 65 and L2 = 50 dB SPL. A suppressor tone was presented at frequencies ranging from 1 octave below to 1/4 octave above f2 and varied in level until DPOAE amplitude was reduced by 6 dB. The suppressor level required for 6 dB suppression was plotted as function of suppressor frequency to generate a DPOAE STC. Forward-masked psychoacoustic tuning curves (PTC) were obtained for three of the adult subjects. Results indicate that DPOAE STCs are stable and show minimal inter- and intra-subject variability. The tip of the STC is consistently centered around the f2 region and STCs are similar in shape, width (Q10) and slope to VIIIth-nerve TCs. PTCs and STCs measured in the same subject showed similar trends, although PTCs had narrower width and steeper slope. Neonatal STCs were recorded at 3000 and 6000 Hz only and were comparable in shape, width and slope to adult STCs. Results suggest: (1) suppression of the 2f1-f2 DPOAE may provide an indirect measure of cochlear frequency resolution in humans and (2) cochlear tuning, and associated active processes in the cochlea, are mature by term birth for at least mid- and high-frequencies. These results provide significant impetus for continued study of DPOAE suppression as a means of evaluating cochlear frequency resolution in humans.

Considering distortion product otoacoustic emission fine structure in measurements of the medial olivocochlear reflex.

In humans, when the medial olivocochlear (MOC) pathway is activated by noise in the opposite ear, changes in distortion product otoacoustic emission (DPOAE) level, i.e., the MOC reflex, can be recorded in the test ear. Recent evidence suggests that DPOAE frequency influences the direction (suppression/enhancement) of the reflex. In this study, DPOAEs were recorded at fine frequency intervals from 500 to 2500 Hz, with and without contralateral acoustic stimulation (CAS) in a group of 15 adults. The MOC reflex was calculated only at DPOAE frequencies corresponding to peaks in the fine structure. Additionally, inverse fast-Fourier transform was conducted to evaluate MOC effects on individual DPOAE components. Results show the following: (1) When considering peaks only, the mean MOC reflex was -2.05 dB and 97% of observations reflected suppression, (2) CAS reduced distortion characteristic frequency component levels more than overlap component levels, and (3) CAS produced an upward shift in fine structure peak frequency. Results indicate that when the MOC reflex is recorded at DPOAE frequencies corresponding to fine structure maxima (i.e., when DPOAE components are constructive and in phase), suppression is reliably observed and level enhancement, which probably reflects component mixing in the ear canal rather than strength of the MOC reflex, is eliminated.

Maturation of medial efferent system function in humans

Otoacoustic emissions are typically reduced in amplitude when broadband noise is presented to the contralateral ear. This contralateral suppression is attributed to activation of the medial olivocochlear system, which has an inhibitory effect on outer hair-cell activity. By studying the effects of contralateral noise on cochlear output at different stages of auditory maturation in human neonates, it is possible to describe the timecourse for development of medial efferent system function in humans. The present study recorded 2 f1-f2 distortion product otoacoustic emissions (DPOAE) in human adults, term and premature neonates at three f2 frequencies: 1500, 3000, and 6000 Hz, using fixed primary tone frequency ratio (f2/f1 = 1.2) and level separation (10 dB, L1 > L2). Average DPOAE growth functions were recorded with and without contralateral broadband noise. Results indicate that contralateral suppression of DPOAEs is absent at 6000 Hz, but present at 1500 and 3000 Hz for all ages. However, DPOAE amplitude from premature neonates was not altered by noise in an adult-like manner; in this age group, DPOAE amplitude was equally likely to by suppressed or enhanced by noise presented contralaterally. Contralateral enhancement may reflect a temporary stage of immaturity in outer hair cell-medial efferent fiber synapses just prior to term birth.

A developmental study of distortion product otoacoustic emission (2f1-f2) suppression in humans

Suppression of the 2f1-f2 distortion product otoacoustic emission (DPOAE) provides an effective paradigm for the study of functional cochlear maturation in humans. DPOAE iso-suppression tuning curves (STCs) represent some aspect of peripheral filtering, probably related to the boundaries of distortion generation. Studies conducted thus far suggest that the cochlear tuning assessed by this technique is adult-like in humans by term birth (Abdala et al., Hear. Res. 98 (1996) 38-53; Abdala and Sininger, Ear Hear. 17 (1996) 374-385). However, there have been no studies of cochlear tuning in premature human neonates. DPOAE STCs and suppression growth functions were measured from 14 normal-hearing adults, 33 term and 85 premature neonates to investigate the developmental time course of cochlear frequency resolution and non-linearity. Premature neonates showed non-adult-like DPOAE suppression at f2 of 1500 and 6000 Hz: (1) STCs were narrower in width (Q10) and steeper in slope on the low-frequency flank of the tuning curve; (2) suppressor tones lower in frequency than f2 produced atypically shallow growth of DPOAE suppression. The influence of immature conductive pathways cannot be entirely ruled out as a factor contributing to these results. However, findings may indicate that an immaturity exists in cochlear frequency resolution and non-linearity just prior to term birth. The bases of this immaturity are hypothesized to be outer hair cell in origin.

The development of frequency resolution in humans as revealed by the auditory brain‐stem response recorded with notched‐noise masking

Studies of tuning in infants have reported that auditory brain-stem response (ABR) tuning curves generated using low-frequency probes are adultlike by 3 months of age while high-frequency tuning curves remain immature [Folsom and Wynne, J. Acoust. Soc. Am. 81, 412-417 (1987)]. Behavioral studies have similarly reported adultlike low-frequency psychoacoustic tuning curves by 3 months with high-frequency tuning curves immature until approximately 6 months of age [L. Olsho, Infant Behav. Dev. 8, 371-384 (1985); Spetner and Olsho, Child Dev. 61, 632-652 (1990); Schneider et al., J. Exp. Psych.: Human Percept. Perform. 16, 642-652 (1990)]. Prior to this experiment, there have been no ABR studies of the development of frequency resolution for infants older than 3 months. In this study, notched-noise tuning functions were constructed from wave-V amplitude data for 3-month-old, 6-month-old, and adult subjects. Tone-pip stimuli at 1000, 4000, and 8000 Hz (50 dB nHL) were presented simultaneously with notched-noise masking centered at frequencies related to the tone-pip frequency (1/3-oct intervals above and below the probe frequency). By plotting wave-V amplitude across notched-noise center frequency, isointensity tuning functions were generated for the three subject groups at the three probe frequencies. Auditory filter width (Q) and slope (dB/oct) were measured from each notched-noise tuning function in order to qualify degree of tuning. Consistent with previous studies, results showed that 3-month-old infants do not have adultlike tuning for high-frequency stimulation (8000 Hz). In contrast, by 6 months of age, tuning-function width (Q) is adultlike for both high- and low-frequency probes. These results, combined with previously reported evidence that the human cochlea is fully tuned at birth [Abdala et al., submitted to Hear. Res. (1995); Bargones and Burns, J. Acoust. Soc. Am. 83, 1809-1816 (1988)], suggest that immaturities in the auditory-neural system contribute to the broad high-frequency tuning consistently observed in 3-month-old human infants.

Theory of forward and reverse middle-ear transmission applied to otoacoustic emissions in infant and adult ears.

The purpose of this study is to understand why otoacoustic emission (OAE) levels are higher in normal-hearing human infants relative to adults. In a previous study, distortion product (DP) OAE input/output (I/O) functions were shown to differ at f2 = 6 kHz in adults compared to infants through 6 months of age. These DPOAE I/0 functions were used to noninvasively assess immaturities in forward/reverse transmission through the ear canal and middle ear [Abdala, C., and Keefe, D. H., (2006). J. Acoust Soc. Am. 120, 3832-3842]. In the present study, ear-canal reflectance and DPOAEs measured in the same ears were analyzed using a scattering-matrix model of forward and reverse transmission in the ear canal, middle ear, and cochlea. Reflectance measurements were sensitive to frequency-dependent effects of ear-canal and middle-ear transmission that differed across OAE type and subject age. Results indicated that DPOAE levels were larger in infants mainly because the reverse middle-ear transmittance level varied with ear-canal area, which differed by more than a factor of 7 between term infants and adults. The forward middle-ear transmittance level was -16 dB less in infants, so that the conductive efficiency was poorer in infants than adults.

Distortion product otoacoustic emission (2f1-f2) amplitude growth in human adults and neonates

Distortion product otoacoustic emissions (DPOAEs) are thought to be by-products of an active amplification process in the cochlea and thus serve as a metric for evaluating the integrity of this process. Because the cochlear amplifier functions in a level-dependent fashion, DPOAEs recorded as a function of stimulus level (i.e., a DPOAE growth function) may provide important information about the range and operational characteristics of the cochlear amplifier. The DPOAE growth functions recorded in human adults and neonates may provide information about the maturation of these active cochlear processes. Two experiments were conducted. Experiment I included normal-hearing adults and term-born neonates. The 2f1-f2 DPOAE growth functions were recorded for both age groups at three f2 frequencies. Experiment II was an extension of the first experiment but added a subject group of premature neonates. The results of these studies indicate that DPOAE growth functions most often show amplitude saturation and nonmonotonic growth for all age groups. However, premature neonates show monotonic growth and the absence of amplitude saturation more often than adults. Those premature neonates who do show saturation also show an elevated threshold for amplitude saturation relative to adults. In contrast, term neonates are adultlike for most measures except that they show a larger percentage of nonsaturating growth functions than adults. These results may indicate immaturity in cochlear amplifier function prior to term birth in humans. Outer hair cell function and/or efferent regulation of outer hair cell function are hypothesized sources of this immaturity, although some contribution from the immature middle ear cannot be ruled out.