MATERIAL AN D METHODS

The effects of contralateral acoustic stimulation on

Normals. Normal subjects were admitted to the study from healthy Volunteers if they had no history of hearing disorder, normal otoscopy, pure tone thresholds < 20 dB HL (0.25-8 kHz), and normal tympanometry ( ± 50 mm HjO middle ear pressure, 0.3-1.5 ml compliance). Eight subjects (20 -4 3 years, 2 male, 6 female) with pure tone thresholds less than or equal to 20 dB HL, normal ipsilateral and con­ tralateral acoustic reflex thresholds between 8 0 - 105 dB (0 .5 -4 kHz), and with no history of hearing disorder were admitted to the study. CEOAE were present bilaterally with amplitudes for the whole non­ linear response (2.5-20 ms) from 8 to 22 dB spl in response to 80-86 dB spl peak level stimuli.

Vestibular neurectomy patients. The selection crite­ ria for vestibular neurectomy patients required nor­ mal otoscopy and tympanometry as defined above. Post-operative pure tone audiometric thresholds (0.25-8 kHz) were required to be within 15 dB or better than preoperative levels. In order to reliably record OAE, thresholds better than 35 dB HL at a minimum of two adjacent frequencies were required. Patients were also selected on the basis of normal auditory evoked brainstem potentials for both abso­ lute and inter-wave latencies (Wave I: 1.3-1.9 ms, III: 3.3-4.1 ms, V: 5.2-6.0 ms; Inter-Waves I-III: 1.6-2.4 ms, III-V; 1.4-2.2 ms, I-Y : 3.6-4.4m s). Vestibular function examinations including electro- nystagmographic (ENG) recordings o f horizontal eye movements, and the Fitzgerald-Hallpike bithermal caloric test confirmed peripheral vestibular disorder. CT scans, CT air meatography, and MRI scans were performed in order to exclude central lesions, and/or to confirm the diagnosis. Only those patients with no evidence of central pathologies were considered for this study.

Over half of the 72 cases undergoing vestibular neurectomy during the past 6 years suffer from Me­ niere’s disease with thresholds of 35 dB HL or better pre-operatively, and two of these patients (32-43 years, females) with recurrent peripheral vestibular dysfunction but with good hearing function, normal

Acta Otolaryngol (Stockh) 114 E ffect o f O C B section on O A E in hum ans 123

15 dB. Otoacoustic emissions were present bilaterally with amplitudes and frequency spectra consistent with pure tone hearing levels. Click stimuli levels of 83 dB spl produced non-linear CEOAE whole echo amplitudes of 13.0 dB, 94% reproducible, A-B 0.9 dB from the operated ear; levels of 80 dB spl produced CEOAE with amplitudes of 10.2 dB, 85% repro­ ducible, A-B 2.3 dB from the intact ear. Neurectomy cases with good hearing levels at all frequencies are most uncommon, and this case provided a rare op­ portunity to conduct a more thorough examination of the effect of de-efferentation on hearing, and the effect of contralateral acoustic stimulation on oto­ acoustic emissions as a function of intensity and frequency.

Case ii maintained post-operative pure tone hear­ ing levels between 25-35 dB HL on the operated side, and 10-25 dB HL on the intact side for frequencies between 0.25-8 kHz. Otoacoustic emissions were present bilaterally, with non-linear CEOAE ampli­ tudes of 5.7 dB, 59% reproducible, A-B 3.1 dB with 87 dB spl click stimuli to the operated side, and 5.3 dB, 65% reproducible, A-B 1.7 dB with 82 dB spl stimulus levels on the intact side. At the time of submission, it had not been possible to obtain pre- and post-operative data from the same patient, but our ongoing research is addressing this comparison.

Vascular decompression patients. Patients who un­ derwent retrolabyrinthine surgery for vascular de­ compression of the V lllth cranial nerve, formed a control group. They were admitted to the study from the surgical population according to the same criteria as the neurectomy group, having normal otoscopy, tympanometry and pure tone thresholds better than 35 dB HL at a minimum of two adjacent frequencies, which remained within 15 dB of pre-operative levels. The selected cases also demonstrated auditory evoked brainstem potentials within the normal limits noted above for both absolute and interwave latency. CT scans, CT air meatography and M RI scans were

remained the same. Thresholds in the operated side were 5-15 dB before surgery and decreased post­ operatively by 5-10 dB from 0 .5 -2 kHz with no change at the other frequencies. Pre-operative CEOAE amplitudes from the operated side produced 13.4 dB, 90% reproducible, A-B 3.6 dB with 88 dB spl click stimuli, and the intact side were 14.5 dB, 95% reproducible, A-B 1.4 dB with 86 dB spl stimu­ lation. Post-operative CEOAE amplitudes on the op­ erated side measured 12.0 dB, 89% reproducible with A-B 2.8 dB with 87 dB spl stimulation. Case D also had normal pure tone audiometry, with thresholds better than 20 dB HL for all frequencies tested (0.25- 8 kHz) and no loss in function following surgery, thresholds varying 5-10 dB around the pre-operative values. CEOAE from the operated side were 17.7 dB spl, 97% reproducible, A-B —5.1 dB with 85 dB spl stimulation, and 14.4 dB, 95% reproducible, A-B 0.7 dB with 85 dB spl stimulation of the intact side. Case B had pre-operative hearing levels from 0 - 15 dB on the intact side which varied by at most 5 dB following surgery. The operated side had thresholds from 5-25 dB, with 4 and 8 kHz being less sensitive. Post-operative values varied from 0 -1 0 dB of the pre-operative thresholds except for 4 and 8 kHz val­ ues which decreased by 15 and 20 dB. CEOAE were present in both ears with amplitudes of 7.7 dB, 59% reproducible, A-B 4.9 dB from the operated side with 83 dB spl click stimuli, and emissions of 9.5 dB, 75% reproducible, A-B 4.2 dB in the intact side with stim­ uli at 80 dB.

Surgical procedure. The retrolabyrinthine surgical approach to the cerebello-pontine angle was per­ formed for both patient groups, as described by Silverstein & Norell (20). Vestibular neurectomy per­ formed at this site removes both medial and lateral components of the olivocochlear bundle traveling within the inferior vestibular nerve. The patients made an uncomplicated recovery, with no evidence of facial nerve compromise. Audiometric profiles,

124 E. A. Williams et al. Acta Otolaryngol (Stockh) 114 IL088 acoustic emission analyzer as described by

Kemp et al. (21). Spectral analysis and amplitude measurement of the responses was performed by the system. The IL088 probe was positioned in the exter­ nal meatus and adjusted to ensure that the power of the frequency spectrum of the click stimulus was as equal as possible across the frequency range of 0 .5 - 3.0 kHz. The OAE responses to 260 clicks were aver­ aged, with and without use of the artifact rejection facility, at peak stimulus levels of 88 dB spl to 61 dB spl, followed by the “efferent test” procedures. The probe position remained stable, and was not adjusted or removed until the recording process was completed for the test ear.

E fferent test procedures. The contralateral stimulus was white noise generated by a Madsen OB802 au­ diometer via a TD K 39 earphone. The patients per­ ceptual threshold to white noise was measured for each ear. The IL088 was set to present OAE click stimuli at 61 dB spl ( ± 2 dB) peak reception level in order to minimize interference from middle ear refl­ exes. Ten sets of 60 click responses were averaged and each set recorded separately. With each alternate set of ten recordings, a fixed level of continuous noise was presented to the ear contralateral to the probe. Three to four series were presented for each ear using different intensities of white noise at levels between 15-70 dB HL (equivalent to 5-55 dB sensation level (SL) above threshold). Contralateral stimuli were chosen to be at least 15 dB less than the individual’s acoustic reflex threshold to white noise. The re­ sponses in quiet (no contralateral stimulus) and in noise (with contralateral white noise) were averaged into separate buffers. Averaged responses with less than 50% reproducibility (due to patient movement or environmental noise) were excluded from analysis. To give a measure of suppression, the averaged OAE amplitude of the whole response (5 -2 0 ms) and of 1000 Hz and of 500 Hz frequency bands from 500- 3000 Hz were converted from the dB SPL values calculated by the IL088 spectral analysis system into microPascals, and the relative difference was ex­

whole response (5 -2 0 ms) was associated with a mean decrease of 26.9% (sd 3.0) with 45-55 dB SL; 14.5% (sd 1.2) with 30-40 dB SL; and 8.14% (sd 1.9) with 15-25 dB SL contralateral stimulation. Di­ rect observation of the filtered emission waveform shows a clear difference in peak to peak amplitude and a phase lead of responses recorded with noise versus quiet. A frequency specific inhibitory effect was observed by filtering the click evoked response within 500 Hz bands and comparing the responses recorded in quiet with responses during moderate levels of contralateral white noise (35-45 dB SL). The greatest suppression occurred within the 1.0- 2.5 kHz range, with lesser effects at 0.5-1.0 kHz, and 2.5-3.0 kHz. The mean values of suppression ob­ served in normals {n = 8) was 30.0% (sd 3.35) in the 1.0-1.5 kHz range; 25.7% (sd 2.5) in the 1.5-2.0 kHz range; 23.7% (sd 4.0) in the 2.0-2.5 kHz range; 18.7% (sd 2.8) in the 0.5-1.0 kHz range; and 18.4% (sd 4.5) suppression in the 2.5-3.0 kHz range.

Vestibular neurectom y patients. In all neurectomy patients examined, inhibition of CEOAE amplitude during contralateral stimulation recorded from the ear with severed efferent fibers was negligible in com­ parison with that recorded from the intact side or with normal values.

The findings are readily observed in Case i in whom contralateral stimulation produced virtually no observable change in amplitude or phase of emissions from the cochlea with severed efferent fibers during 25 dB SL noise (showing a decrease of only 4.5% in CEOAE amplitude). In contrast, a clear peak to peak decrease in amplitude equivalent to a 13.9% reduc­ tion, and a phase lead can be observed in the wave­ forms recorded from the intact side with 25 dB SL noise versus those recorded in quiet (Fig. 1). Case ii demonstrated similar results. Suppression of otoa­ coustic emissions was absent (0.0% change) from the operated side with moderate levels of contralateral stimulation (45 dB SL), whilst CEOAE amplitude from the intact side decreased by 11.9% from ampli­ tudes recorded in quiet (Fig. 2).

Acta O tolaryngol (Stockh) 114 Effect o f O C B section on O A E in humans 125

IQms

Fig. I. V estibular neurectom y C ase i. T he effect o f c o n tralateral w hite noise on click evoked O A E w aveform s. The intact side {left trace) show s a decrease in peak to peak am p litu d e an d a phase lead o f the filtered (1000 H z b and) w aveform recorded in 25 dB SL noise (tra c e A) relative to quiet co n d itio n s (B). T he op erated side (right trace) show s virtually no observable difference in am plitude o r phase o f filtered w aveform s recorded w ith o u t o r w ith 25 dB SL o f co n tralateral noise.

* 1 6

Fig. 2. V estibular neurectom y C ase ii. S uperim posed filtered O A E from the o p erated side (right trace) d em o n strates the lack o f in ter-au ral suppression follow ing neurectom y with 45 dB SL c o n tralateral noise. Inh ib itio n o f O A E am p litu d e with co n tralateral noise at 45 dB SL was m aintained on the in tact side (left trace).

- -1 0 Z - 2 0

% - 3 0

-4 0 -5 0

Sensation Level of White Noise (dB SL)

N o r m a l I + 2 S D I N e u r e c t o m y i n t a c t

N o r m a l ( - 2 S D I N e u r e c t o m y o p e r a t e d

Fig. 3. Suppression o f O A E am plitude as a function o f co n tralateral stim ulation level follow ing vestibular neurec­ tom y. In com parison w ith norm al m easures (m ean and ± 2 sta n d a rd deviations), C ase i d em o n strates negligible su p ­ pression o f O A E am plitude on the o p erated side (square sym bols), whilst inter-aural suppression is m aintained at

response patterns well above the noise floor within the frequency range of 0.5-3 kHz for which the IL088 microphone response function is relatively constant. Spectral analysis of the emissions within 500 Hz bands from the intact side demonstrated a frequency specific pattern of inhibition with 25-35 dB spl noise which was consistent with our normal results, for all frequen­ cies from 0.5-3.0 kHz, except within the 1.0-1.5 kHz band. In contrast, CEOAE suppression in the oper­ ated side was less than 2 standard deviations from the mean observed in normal subjects for all frequency bands measured (Fig. 4).

J

126 E. A. Williams et al. Acta Otolaryngol (Stockh) 114

Vascular decompression patients. In all cases exam­ ined a decrease in amplitude and phase lead was observed in emissions recorded during contralateral stimulation from both operated and intact sides fol­ lowing vascular decompression. Fig. 5 shows the filtered emissions (1000 Hz band) from the operated sides of three cases with the waveforms recorded in noise superimposed over those recorded in quiet. Fig. 6 illustrates the relative decrease in CEOAE ampli­ tude as a function of stimulus intensity for both the operated and intact sides of these cases. CEOAE amplitude recorded in noise was inversely related to the intensity of the contralateral stimuli. Suppression was induced with contralateral stimulation greater than 15 dB SL (30 dB HL), and was comparable for both sides, showing a drop in CEOAE amplitude from 10.87% with 30 dB SL to a maximum decrease of 31.61% with 45 dB SL (35-65 dB HL). These values of inhibition were within at least 2 standard deviations of the range recorded in normals.

The emissions from Case P showed that 35 dB SL contralateral noise was associated with inter-aural suppression of equivalent magnitude (18.72%) in both the operated and intact sides. This patient was

- 1 0 Z - 2 0 O - 3 0 - 4 0 O - 5 0 # (0 5 10 15 20 25 30 35 40 46 50 65 60 S en satio n Level of W hite Noise (dB SL)

+ N o r m a l ( + 2 S D I + N o r m a l ( - 2 S D ) N o r m a l M e a n V a s e . D e c . P - R - o - V a s e . D e e . P - L - w - V a s e . D e e . D - R - # - V a s e . D e e . D L V a s e . D e e . B - L

Fig. 6. Suppression of OAE amplitude as a function of

contralateral stimulation level following vascular decom­ pression. The relative suppression of OAE amplitude (% change of amplitude in noise versus quiet) as a function of contralateral stimulation is illustrated for the operated and intact sides {R = right, L = left) of Cases D, P, B. The control data is comparable to suppression observed in normals (mean ± 2 standard deviations).

C o cM eir Response C a s e P 4 0 d B S L C a s e B 4 0 d B S L 10MS

A cta Otolaryngol (Stockh) 114 Effect o f OCB section on O A E in humans 127

studied before and following surgery, and demon­ strated that contralateral suppression was maintained relative to pre-operative levels (Fig. 7),

DISCUSSION

The study o f patients undergoing vestibular neurec­ tomy resulting in section o f the efferent olivocochlear bundle traveling within the inferior division o f the vestibular nerve, provides a hum an physiological model for examining the role of the efferent aud­ itory system in controlling cochlear responses (see Williams et al. (19)). Otoacoustic emission measure­ ments demonstrated that in the absence of efferent innervation, contralateral acoustic stimulation had no observable effect on the amplitude or phase o f emis­ sions recorded from ears with severed nerve fibers. In contrast, control information from the patients’ in­ tact side showed that inhibition o f OAE was m ain­ tained, exhibiting a clear phase lead and reduction in ampHtude that was inversely related to the level of contralateral noise intensity and with a frequency specific pattern which was consistent with our norm a­ tive results and with recently reported normal studies (17, 18). These findings suggest that the inhibitory effect of contralateral noise on cochlear emissions was absent as a result of sectioning the efferent olivococh­ lear bundle.

During surgery the isolation of the vestibular nerves is assisted by observation of a fine septum between the cochlear and vestibular nerves in 7 5 % - 80% of patients, however there can be an intermin­ gling of cochlear and vestibular fibers along the apparent line of division, with an overlapping zone occupying approximately 16-33% of the area o f the cochlear subdivision (21). W arren & Liberman (16) provided evidence of the efficacy of vestibular nerve section in routinely interrupting the entire OCB in cats, as demonstrated by the lack o f retrograde la­ beled neurons in the superior olivary complex follow­

In order to assess the impact of retrolabyrinthine surgery on inter-aural suppression of emissions, pa­ tients who had undergone a similar surgical approach for vascular decompression of the V lllth nerve, but without nerve section were studied. In all cases exam­ ined, inter-aural suppression o f OAE was observed in both the operated and intact sides, with OAE ampli­ tude decreasing with increasing contralateral noise levels. Post-operative measures o f OAE amplitude and inhibition were comparable with pre-operative values in the case examined. This further indicates th at the retrolabyrinthine surgery itself need not in­ terfere with inter-aural suppression o f otoacoustic emissions.

Our normal group displayed similar results to the control surgical population. N orm al hearing adults showed that low to moderate levels o f contralateral noise (15-45 dB SL) were consistently associated with inhibition of OAE amplitude. The magnitude of suppression was inversely related to the level of the contralateral stimuli, and was most effective at fre­ quencies above 1 kHz in a broadly tuned pattern. Given that the test measured the effect o f a broad band contralateral noise on a broad band eliciting ipsilateral stimulus, a sharper tuning curve need not be expected.

It has been suggested that the contralateral effect could be a function of the bilateral activation of the acoustic reflexes resulting in reduced transmission of the OAE to the ear canal. To avoid reflex activation, the protocol utilized noise and OAE stimuli at inten­ sity levels below reflex thresholds, although the possi­ bility that the muscles were active below the levels measurable with standard clinical tympanometric devices cannot be entirely excluded. Our results, which show that vestibular neurectomy patients with

intact acoustic reflexes showed negligible suppression

after OCB section, diminishes the possibility that the effect is mediated solely via the middle ear muscles. Other studies have dem onstrated that the effect of

1 2 8 E. A. W illiams et al. Acta Otolaryngol (Stockh) 114 ear activity. In addition, Warren & Liberman (16)

argue that the frequency dependence of the effect is more consistent with the frequency distribution of efferent innervation in the middle range of frequen­ cies, and is incompatible with the acoustic reflex activity which is most effective at a lower frequency