**5.1.1 Materials and methods**

#### **5.1.1.1 Animals**

Ten anaesthetized adult chinchillas (Chinchilla laniger) weights 505 - 725 g were studied. The anesthetic regime was intra-peritoneal Ketamine 15mg/kg (Ketamine Hydrochloride U.S.P. 100mg/ml, Ayerst Laboratories, Ontario), Xylazine 2.5mg/kg (Xylazine 20mg/ml, Bayer Inc., Toronto), and Atropine 0.04mg/kg (Atropine Sulfate 0.5mg/ml, MTC Pharmaceuticals, Ontario). Recordings were started 15 minutes after induction of anesthesia. A second dose of anesthetic was given 45 minutes later (intra-peritoneal Ketamine 8mg/kg, Xylazine 1.3mg/kg). Five animals were studied twice, typically with an interval of >4 weeks between recording sessions. Thus in total, 15 recording sessions were completed. All studies were approved by the local Animal Care Committee, following the guidelines of the Canadian Council on Animal Care.

#### **5.1.1.2 Real time DPOAE measurement**

34 Hearing Loss

neurons have a characteristic frequency (CF) similar to that measured in the cochlear

Frequency specificity of MOCS activity can also be detected when recording the response of inner hair cells and auditory nerve fibers to acoustic stimulation. For example in cats, the response of single cochlear afferent fibers to tone pips is suppressed by simultaneously applying tone pips to the contralateral ear. This suppression is maximal when the contralateral tone is similar to the characteristic frequency of the afferent fiber (Murata, Tanahashi, Horikawa, & Funai, 1980; Warren III & Liberman, 1989a; Warren III & Liberman, 1989b). Similarly, when recording the compound action potential induced by tone pips with a round window electrode, maximum suppression is induced by contralateral tone pips of

As OAEs are generated by OHC activity, they may provide a more direct and non-invasive insight into the effect of the MOCS on its target cells than neural recordings. In human subjects, suppression of spontaneous OAEs is maximal with a CAS tone at a frequency close to the spontaneous OAE (Mott, Norton, Neely, & Bruce Warr, 1989). In addition to suppression, a frequency shift of spontaneous OAEs is caused by CAS and interestingly this is maximal with a CAS about 3/8 to 1/2 octaves below the spontaneous OAE frequency. OAEs evoked by tone pips can be suppressed by contralateral narrow band noise, suppression being maximal with CAS frequencies close to the frequency of the tone pip

Contralateral suppression of OAEs has not been widely used to investigate MOCS frequency specificity in animal models. A systematic study in the barn owl produced frequency response functions in which DPOAE suppression was plotted as a function of CAS frequency (Manley, Taschenberger, & Oeckinghaus, 1999). This showed maximal suppression with CAS similar to primary frequencies. Extrapolation of these findings to other models is limited by the variability of DPOAE levels and the additional types of

The purpose of the present study was to investigate the frequency specificity of the MOCS in the chinchilla. In this species there has been a report of difficulty in detecting MOCS change in response to contralateral stimulation (Azeredo et al., 1999). On the other hand, electrical stimulation of the olivocochlear bundle in the floor of the fourth ventricle elicits OAE suppression (Siegel & Kim, 1982). In our present study, the suppressive effect on DPOAEs of contralateral pure tone stimuli is investigated with real-time recording of the

Ten anaesthetized adult chinchillas (Chinchilla laniger) weights 505 - 725 g were studied. The anesthetic regime was intra-peritoneal Ketamine 15mg/kg (Ketamine Hydrochloride U.S.P. 100mg/ml, Ayerst Laboratories, Ontario), Xylazine 2.5mg/kg (Xylazine 20mg/ml, Bayer Inc., Toronto), and Atropine 0.04mg/kg (Atropine Sulfate 0.5mg/ml, MTC Pharmaceuticals, Ontario). Recordings were started 15 minutes after induction of anesthesia. A second dose of anesthetic was given 45 minutes later (intra-peritoneal Ketamine 8mg/kg,

efferent.

DPOAE.

**5.1.1.1 Animals** 

similar frequency (M. C. Liberman, 1989).

(Veuillet, Collet, & Duclaux, 1991).

efferent fiber which are present in birds.

**5.1.1 Materials and methods** 

DPOAEs were measured in real time with a Vivo 600 DPR device (Vivosonic Inc., Toronto, ON). In contrast to conventional OAE techniques which employ signal averaging to extract the signal from noise, this technique uses digital filtering and signal modeling. The continuous real-time signal is ideally suited to the detection of changes in OAE amplitude, such as those produced by contralateral stimuli (James et al., 2005). Primary frequencies were set at f2/f1= 1.22 for values of f2 between 1.6 and 8.0 kHz, with intensities of L1 = 70dB and L2 = 65dB. DPOAEs were measured at 2f1-f2. The OAE probe, in a conforming soft plastic cuff, was inserted into the external auditory meatus by straightening the soft tissues to allow the probe to abut the lateral aspect of the bony meatus (approximately 13mm from the tympanic membrane). Multiple recordings of up to three minutes duration were made in each session. All recordings were made in a sound-attenuating booth. The DPOAE probe was calibrated in the ear canal by the device and calibration confirmed in a 2ml coupler using an SR760 FFT Spectrum Analyzer (Stanford Research Systems, Sunnyvale, CA) and a precision CR: 511D Acoustic Calibrator (Cirrus Research plc, North Yorkshire, U.K.).

### **5.1.1.3 Contralateral stimulus**

An intermittent pure tone stimulus was applied to the contralateral ear using an ER-2 transducer with a foam ear-insert (Etymotic Research Inc., IL). 60 different CAS frequencies were tested between 0.6 – 17 kHz. Sweep direction from high to low, or low to high frequency of contralateral stimulation was changed between sweeps to control for any gradual drift in DPOAE level that might occur during a recording period. CAS intensity was set at 50 dB SPL as a previous study had shown the threshold for a response to be around 30dB SPL while acoustic cross talk occurred at intensities of ≥70 dB SPL (using noise floor measures and recordings in cadaveric chinchilla). Stimulus duration was set at 0.5s with rise / fall times of 4 ms. The interval between stimuli was long enough to allow DPOAE levels to return to pre-stimulus levels (typically > 300ms longer than CAS duration).

### **5.1.1.4 Analysis of results**

DPOAE signals were recorded in real time, and level changes occurring in synchrony with contralateral stimulation were noted. Subsequent analysis was performed on the recorded real time trace and on averaged data, using VivoAnalysis software (Vivosonic Inc., ON), based on LabVIEW 5.1 data acquisition software (National Instruments, TX). Averaging was synchronized with the start of the CAS and was used to smooth the data and remove nonsynchronous or spontaneous variation in the DPOAE signal. Averaged data were used to measure the magnitude of the DPOAE response to CAS from the baseline (no contralateral stimulation condition) to maximum OAE change (i.e. at asymptotic level). Frequency response curves to indicate tuning of contralateral suppression were plotted with magnitude of suppression (dependent variable) versus frequency of CAS tone (independent variable).

Contralateral Suppression of Otoacoustic Emissions:

Change in DPOAE level (dB)

indicating the frequency dependence of DPOAE suppression.

Working Towards a Simple Objective Frequency Specific Test for Hearing Screening 37

Typical examples of averaged DPOAE suppression responses are shown in figure 2. Here the DPOAE measured is at f2 = 4.4 kHz, with contralateral suppression stimuli between 2.8 and 6.7 kHz. In this series, suppression is greatest (0.8 dB) with contralateral stimulations at 4.5 kHz, but is only half this value when contralateral stimulation is at 2.8 kHz or 6.7 kHz,

> Suppression tone frequency

> > 2.8kHz

3.7kHz

4.5kHz

5.9kHz

6.7kHz

Fig. 2. Averaged DPOAE signal from 20s recording periods, synchronized with onset of contralateral stimulus. (DPOAE at f2 = 4.4 kHz; contralateral acoustic stimulation at

Time (s)

DPOAE f2 = 4.4kHz

frequencies of 2.8 – 6.7 kHz (550ms duration, as black bar).

#### **5.1.2 Results**

DPOAEs were successfully recorded in real time in all animals. DPOAE levels were stable for the duration of the experiments, though they tended to fall gradually around 2 – 4 dB/hr. Figures 1 through 5 demonstrate DPOAE suppression data progressing from the initial real time signal, to the averaged waveform, and finally ideal curve fitting to the contralateral frequency response function.

Fig. 1. Typical example of contralateral suppression of real time DPOAE signals in chinchilla: (a) DPOAE at f2 = 4.4 kHz, contralateral acoustic stimulation = 5.9 kHz at 50dB SPL; (b) DPOAE at f2 = 7.7 kHz, contralateral acoustic stimulation = 8.4 kHz at 50 dB SPL. (Stimulus duration = 550ms, marked by horizontal black bar).

Figure 1 shows examples of real time recordings of DPOAE suppression. Panel 1a shows variation in DPOAE level at f2 = 4.4 kHz over a twelve second period during six periods of CAS at 5.9 kHz (marked by horizontal bar). Suppression of 0.5 dB from the baseline level of 38.8 dB SPL occurs with each CAS. In panel 1b, a DPOAE at f2 = 7.7 kHz is suppressed by 1.2 dB by CAS of 8.4 kHz. The suppression response was sometimes smaller than the spontaneous signal variation so was not always readily visible in real-time. However, by averaging the raw real-time data in synchrony with the onset of CAS, suppression could usually be detected.

DPOAEs were successfully recorded in real time in all animals. DPOAE levels were stable for the duration of the experiments, though they tended to fall gradually around 2 – 4 dB/hr. Figures 1 through 5 demonstrate DPOAE suppression data progressing from the initial real time signal, to the averaged waveform, and finally ideal curve fitting to the

Fig. 1. Typical example of contralateral suppression of real time DPOAE signals in chinchilla: (a) DPOAE at f2 = 4.4 kHz, contralateral acoustic stimulation = 5.9 kHz at 50dB SPL; (b) DPOAE at f2 = 7.7 kHz, contralateral acoustic stimulation = 8.4 kHz at 50 dB SPL.

Figure 1 shows examples of real time recordings of DPOAE suppression. Panel 1a shows variation in DPOAE level at f2 = 4.4 kHz over a twelve second period during six periods of CAS at 5.9 kHz (marked by horizontal bar). Suppression of 0.5 dB from the baseline level of 38.8 dB SPL occurs with each CAS. In panel 1b, a DPOAE at f2 = 7.7 kHz is suppressed by 1.2 dB by CAS of 8.4 kHz. The suppression response was sometimes smaller than the spontaneous signal variation so was not always readily visible in real-time. However, by averaging the raw real-time data in synchrony with the onset of CAS, suppression could

(Stimulus duration = 550ms, marked by horizontal black bar).

usually be detected.

**5.1.2 Results** 

contralateral frequency response function.

Typical examples of averaged DPOAE suppression responses are shown in figure 2. Here the DPOAE measured is at f2 = 4.4 kHz, with contralateral suppression stimuli between 2.8 and 6.7 kHz. In this series, suppression is greatest (0.8 dB) with contralateral stimulations at 4.5 kHz, but is only half this value when contralateral stimulation is at 2.8 kHz or 6.7 kHz, indicating the frequency dependence of DPOAE suppression.

Fig. 2. Averaged DPOAE signal from 20s recording periods, synchronized with onset of contralateral stimulus. (DPOAE at f2 = 4.4 kHz; contralateral acoustic stimulation at frequencies of 2.8 – 6.7 kHz (550ms duration, as black bar).

Contralateral Suppression of Otoacoustic Emissions:

Working Towards a Simple Objective Frequency Specific Test for Hearing Screening 39

Fig. 4. Contralateral suppression frequency response curve for DPOAE of f2 = 4.4 kHz (marked by vertical dotted line), derived from pooling data from 8 animals. Bars show 95%

in figure 3, the curve peaks near the f2 frequency (dotted line).

The frequency response function for f2 = 4.4 kHz in figure 4 was derived from 22 recordings in eight animals. Mean suppression was plotted against CAS frequency. The large 95% confidence intervals reflect the variability of response in different experiments. However, as

Contralateral stimulus frequency (kHz)

In figure 3, magnitude of contralateral suppression is plotted against CAS frequency for six different DPOAE frequencies. The curves peak close to the f2 value (marked by the dotted line) but typically peak suppression magnitude occurs at a frequency slightly higher than f2.

confidence intervals.

DPOAE suppression (dB)

Fig. 3. DPOAE suppression plotted against contralateral stimulation frequency. Panels a – f show suppression response measured from single animal recordings at DPOAE frequencies ranging from f2 of 1.6 kHz to 7.7 kHz.

f2 = 1.6kHz f2 = 2.2kHz (a) (b)

(c) (d)

(e) (f)

Fig. 3. DPOAE suppression plotted against contralateral stimulation frequency. Panels a – f show suppression response measured from single animal recordings at DPOAE frequencies

Contralateral stimulus frequency (kHz)

f2 = 5.4kHz f2 = 7.7kHz

f2 = 3.1kHz f2 = 4.4kHz

ranging from f2 of 1.6 kHz to 7.7 kHz.

DPOAE suppression (dB)

Fig. 4. Contralateral suppression frequency response curve for DPOAE of f2 = 4.4 kHz (marked by vertical dotted line), derived from pooling data from 8 animals. Bars show 95% confidence intervals.

The frequency response function for f2 = 4.4 kHz in figure 4 was derived from 22 recordings in eight animals. Mean suppression was plotted against CAS frequency. The large 95% confidence intervals reflect the variability of response in different experiments. However, as in figure 3, the curve peaks near the f2 frequency (dotted line).

In figure 3, magnitude of contralateral suppression is plotted against CAS frequency for six different DPOAE frequencies. The curves peak close to the f2 value (marked by the dotted line) but typically peak suppression magnitude occurs at a frequency slightly higher than f2.

Contralateral Suppression of Otoacoustic Emissions:

respectively, 1.7, 1.8, 1.4, 1.15, and 1.3 octaves.

analysis as they may represent a different process.

Working Towards a Simple Objective Frequency Specific Test for Hearing Screening 41

amplitude) bandwidth values for suppression curves at 3.1, 4.4, 5.4, 6.6, and 7.7 kHz (f2) are,

DPOAE suppression was seen in all animals with contralateral pure tone stimulation. On rare occasions, CAS induced an increase in DPOAE level. This occurred at f2 = 2.2 kHz in one chinchilla and at f2 = 6.6 and 7.7 kHz in another. The maximum response occurred with a contralateral tone at or just below the frequency of f2. These data were excluded from

Fig. 6. Regression functions (Weibull) of DPOAE suppression frequency response curves for four values of f2 between 3.1 and 7.7 kHz. Curves are plotted on an absolute dB suppression

scale.

In an attempt to reduce the variability of the response between recordings and to obtain finer details on the shape of the frequency response, repeated measures from CAS close to f2 were made in successive recordings in one chinchilla. The results are shown in figure 5. Even within this single recording period in an individual animal, variability (up to 0.15dB) can be seen in successive sweeps. No repeatable notches in the curve were visible.

As illustrated in figure 5 by the continuous line, the general shape of the DPOAE suppression tuning can be characterized by fitting a regression curve to the data. In figure 6, the same regression function is plotted for four values of f2 between 3.1 – 7.7 kHz using data combined from multiple recordings. The responses are asymmetric with a tendency to drop off more steeply at values of CAS greater than f2. Small suppression responses can be obtained by CAS tones more than one octave lower than the f2 frequency.

Fig. 5. Contralateral suppression frequency response curve for DPOAE of f2 = 4.4 kHz derived from one subject. Dashed line is mean value. Solid line is regression curve (Weibull).

In figure 7, the suppression curves of fig. 6 are plotted on a normalized amplitude scale. The curves are broadly tuned and thus there is considerable overlap. The tuning of suppression curves for high frequency DPOAEs is narrower than at lower frequencies. The (half-

In an attempt to reduce the variability of the response between recordings and to obtain finer details on the shape of the frequency response, repeated measures from CAS close to f2 were made in successive recordings in one chinchilla. The results are shown in figure 5. Even within this single recording period in an individual animal, variability (up to 0.15dB)

As illustrated in figure 5 by the continuous line, the general shape of the DPOAE suppression tuning can be characterized by fitting a regression curve to the data. In figure 6, the same regression function is plotted for four values of f2 between 3.1 – 7.7 kHz using data combined from multiple recordings. The responses are asymmetric with a tendency to drop off more steeply at values of CAS greater than f2. Small suppression responses can be

can be seen in successive sweeps. No repeatable notches in the curve were visible.

Fig. 5. Contralateral suppression frequency response curve for DPOAE of f2 = 4.4 kHz derived from one subject. Dashed line is mean value. Solid line is regression curve

In figure 7, the suppression curves of fig. 6 are plotted on a normalized amplitude scale. The curves are broadly tuned and thus there is considerable overlap. The tuning of suppression curves for high frequency DPOAEs is narrower than at lower frequencies. The (half-

(Weibull).

obtained by CAS tones more than one octave lower than the f2 frequency.

amplitude) bandwidth values for suppression curves at 3.1, 4.4, 5.4, 6.6, and 7.7 kHz (f2) are, respectively, 1.7, 1.8, 1.4, 1.15, and 1.3 octaves.

DPOAE suppression was seen in all animals with contralateral pure tone stimulation. On rare occasions, CAS induced an increase in DPOAE level. This occurred at f2 = 2.2 kHz in one chinchilla and at f2 = 6.6 and 7.7 kHz in another. The maximum response occurred with a contralateral tone at or just below the frequency of f2. These data were excluded from analysis as they may represent a different process.

Fig. 6. Regression functions (Weibull) of DPOAE suppression frequency response curves for four values of f2 between 3.1 and 7.7 kHz. Curves are plotted on an absolute dB suppression scale.

Contralateral Suppression of Otoacoustic Emissions:

1.7 and 1.8 octaves at 3.1 and 4.4 kHz.

localization tasks.

**6. Conclusions** 

Working Towards a Simple Objective Frequency Specific Test for Hearing Screening 43

MOCS frequency tuning has been assessed in the cat by recording changes in single afferent fiber activity during CAS. Suppression of afferent firing rate is maximal with a CAS of similar frequency to the characteristic frequency of the afferent fiber (Warren III & Liberman, 1989a; Warren III & Liberman, 1989b)). Tuning of this form of contralateral suppression was asymmetric, falling off more sharply at CAS frequencies above characteristic frequency, and were much less sharp than afferent tuning. Tuning tended to be sharper at higher frequencies. These observations in the cat are consistent with the contralateral DPOAE suppression tuning reported here for the chinchilla, where bandwidths for curves at 6.6 and 7.7 kHz (f2) are 1.15 and 1.3 octaves respectively, but are

As shown by others, the primary tones used to generate DPOAE stimulate the MOCS and so cause ipsilateral DPOAE suppression (Guinan, Backus, Lilaonitkul, & Aharonson, 2003; M. C. Liberman, Puria, & Guinan Jr., 1996). It can be expected that the primary tones would suppress cochlear function in the contralateral ear by MOCS activation, with the same broad frequency tuning that we have observed. Given that the magnitude of contralateral suppression of DPOAE is dependent upon intensity of the contralateral stimulus (A. James, Mount, & Harrison, 2002), a hypothetical outcome would be a notch in the frequency response curve at the primary frequencies, f1 and f2. This has been observed at f1 in the barn owl but despite thorough investigation at one frequency (f2 = 4.4kHz, figure 5), we were

As in other studies, recordings were completed under anesthesia with ketamine and xylazine. This does reduce the magnitude of contralateral suppression of DPOAE and other measures of olivocochlear function but facilitates recording by providing stable recording conditions, with less behavioral noise and movement artifact (Cazals & Huang, 1996; da Costa, Erre, de Sauvage, Popelar, & Aran, 1997; Harel, Kakigi, Hirakawa, Mount, & Harrison, 1997). We have not investigated the effect of anesthesia on tuning sharpness.

As mentioned previously the exact function of the medial olivo-cochlear system remains speculative. Because of the predominantly inhibitory effect seen on outer hair cell function, improved detection of sound in noise or a protective effect have been hypothesized. Any role postulated for the contralateral suppression response should take into account the relatively slow dynamic of this reflex, being of the order of 26ms in chinchilla and 45ms in humans (James, Harrison, Pienkowski, Dajani, & Mount, 2005). The presence of a response from low intensity contralateral stimuli suggests the function of this system is less likely a protective one, but more to do with frequency tuning of the afferent neural responses via efferent effects on OHC motility. The efferent system may function as a gain control with a long time-constant, equalizing sensitivity between the ears. The optimal condition for detecting inter-aural timing or intensity differences would perhaps be when the two ears have equivalent function. In this respect, the medial contralateral efferent system may also have a role in "balancing" the ears such as to improve the accuracy of these binaural sound

Objective tests such as OAE and ABR are widely used in hearing screening programs and have lead to great advances in the early detection and rehabilitation of neonatal hearing

unable to demonstrate this phenomenon in the chinchilla (Manley et al., 1999).

Fig. 7. DPOAE suppression frequency response curves (Weibull regressions) for f2 values between 3.1 and 7.7 kHz, plotted on a normalized suppression scale (data from figs 4 and 6).

#### **5.1.3 Discussion**

This study demonstrates that suppression of DPOAEs by contralateral pure tones can be detected in the chinchilla with real time recording. DPOAE suppression is greatest when using contralateral stimulation tones close to primary tone f2. This tonotopic response is consistent with other investigations of frequency specificity in the MOCS pathway (Chery-Croze, Moulin, & Collet, 1993; Cody & Johnstone, 1982; M. C. Liberman, 1989; Murata et al., 1980; Robertson, 1984; Robertson & Gummer, 1985; Veuillet et al., 1991; Warren III & Liberman, 1989a; Warren III & Liberman, 1989b). Unlike observations in human subjects, we did not observe any dips in fine structure DPOAEs to account for differences in the magnitude of suppression at different values of f2 or between chinchillas (Wagner, Heppelmann, Müller, Janssen, & Zenner, 2007).

Measurement of contralateral frequency tuning of MOCS fibers has revealed narrow band tuning equivalent in sharpness to cochlear afferent neurons (Brown, 1989; M. Liberman & Brown, 1986; Robertson, 1984). The final, divergent innervation pattern of MOCS fibers at the OHC level appears to degrade this cochleotopicity (or frequency tuning) by a factor of 4- 5 from 0.33 octaves (the approximate bandwidth of auditory afferents) to about 1.7 octaves for f2 = 3.1kHz and 1.3 octaves for f2 = 7.7kHz. The difference in tuning likely rests with the divergent OHC innervation by the MOCS fibers. Neural tracing studies in guinea pig have shown MOCS fibers innervating 15 -61 OHCs (Brown, 1989). In the cat, individual cochlear efferents contact 23 – 84 OHCs spanning 0.55-2.8mm (M. Liberman & Brown, 1986). Thus although tuning in the efferent fibers themselves appears to be as sharp as afferent tuning, the effect of individual fibers on the organ of Corti will be much less precise.

MOCS frequency tuning has been assessed in the cat by recording changes in single afferent fiber activity during CAS. Suppression of afferent firing rate is maximal with a CAS of similar frequency to the characteristic frequency of the afferent fiber (Warren III & Liberman, 1989a; Warren III & Liberman, 1989b)). Tuning of this form of contralateral suppression was asymmetric, falling off more sharply at CAS frequencies above characteristic frequency, and were much less sharp than afferent tuning. Tuning tended to be sharper at higher frequencies. These observations in the cat are consistent with the contralateral DPOAE suppression tuning reported here for the chinchilla, where bandwidths for curves at 6.6 and 7.7 kHz (f2) are 1.15 and 1.3 octaves respectively, but are 1.7 and 1.8 octaves at 3.1 and 4.4 kHz.

As shown by others, the primary tones used to generate DPOAE stimulate the MOCS and so cause ipsilateral DPOAE suppression (Guinan, Backus, Lilaonitkul, & Aharonson, 2003; M. C. Liberman, Puria, & Guinan Jr., 1996). It can be expected that the primary tones would suppress cochlear function in the contralateral ear by MOCS activation, with the same broad frequency tuning that we have observed. Given that the magnitude of contralateral suppression of DPOAE is dependent upon intensity of the contralateral stimulus (A. James, Mount, & Harrison, 2002), a hypothetical outcome would be a notch in the frequency response curve at the primary frequencies, f1 and f2. This has been observed at f1 in the barn owl but despite thorough investigation at one frequency (f2 = 4.4kHz, figure 5), we were unable to demonstrate this phenomenon in the chinchilla (Manley et al., 1999).

As in other studies, recordings were completed under anesthesia with ketamine and xylazine. This does reduce the magnitude of contralateral suppression of DPOAE and other measures of olivocochlear function but facilitates recording by providing stable recording conditions, with less behavioral noise and movement artifact (Cazals & Huang, 1996; da Costa, Erre, de Sauvage, Popelar, & Aran, 1997; Harel, Kakigi, Hirakawa, Mount, & Harrison, 1997). We have not investigated the effect of anesthesia on tuning sharpness.

As mentioned previously the exact function of the medial olivo-cochlear system remains speculative. Because of the predominantly inhibitory effect seen on outer hair cell function, improved detection of sound in noise or a protective effect have been hypothesized. Any role postulated for the contralateral suppression response should take into account the relatively slow dynamic of this reflex, being of the order of 26ms in chinchilla and 45ms in humans (James, Harrison, Pienkowski, Dajani, & Mount, 2005). The presence of a response from low intensity contralateral stimuli suggests the function of this system is less likely a protective one, but more to do with frequency tuning of the afferent neural responses via efferent effects on OHC motility. The efferent system may function as a gain control with a long time-constant, equalizing sensitivity between the ears. The optimal condition for detecting inter-aural timing or intensity differences would perhaps be when the two ears have equivalent function. In this respect, the medial contralateral efferent system may also have a role in "balancing" the ears such as to improve the accuracy of these binaural sound localization tasks.
