Medial Efferent Function Research Articles

Maturation of the human medial efferent reflex revisited

Past work applying otoacoustic emissions to gauge maturational status of the medial olivocochlear (MOC) reflex in human newborns has produced mixed results. The present study revisits the question while considering the dual nature of the 2f(1) - f(2) distortion product otoacoustic emission (DPOAE) and expanding measures of medial efferent function. Subjects included premature and term-born neonates, 6-month-old infants and young adults. The MOC reflex was elicited with contralateral acoustic stimulation (CAS) while shifts in amplitude and phase of the DPOAE, and its distortion and reflection components, were monitored. Overall, CAS-elicited reductions in DPOAE level did not differ among age groups. For all ages, the MOC reflex was strongest at frequencies below 1.5 kHz, and the reflection component of the DPOAE was most affected, showing maximally reduced amplitude and shallower phase slope when contralateral noise was presented. Results suggest that the MOC reflex likely reaches maturation prior to full-term birth. However, prematurely born neonates show markedly more episodes of CAS-induced DPOAE level enhancement. This may be due to more intrusive component mixing in this age group or disruptions in the formation of the MOC pathway or synapse in the most premature neonates.

Relationship between medial‐olivocochlear reflex strength and masked thresholds.

Otoacoustic emission amplitude is reduced by contralateral acoustic stimulation (CAS). This effect is produced by the medial‐olivocochlear (MOC) reflex. Past studies have shown that the MOC reflex is related to listening in noise and selective attention. The present study examined the relationship between the MOC reflex and masked thresholds in 14 normally hearing adults. Detection thresholds were determined for a 1000‐Hz, 300‐ms tone presented simultaneously with a 300‐ms masker. Three masking conditions in which energetic or informational masking predominate were investigated. DPOAEs were evoked from 500–4000 Hz with primary tones swept in frequency at 8 s/oct, using a fixed f2/f1 ratio of 1.22 at 65/55 dB sound pressure level. The MOC reflex and MOC‐shift were measured at DPOAE fine structure maxima at 948 and 1091 Hz with and without CAS. An inverse fast‐Fourier transform was performed to evaluate MOC effects on individual DPOAE components. Preliminary data analyzes showed MOC activity to be correlated with masked thresholds for both indices of medial efferent function. Most notably, higher masked thresholds for the random and broadband conditions were associated with a stronger MOC reflex for DPOAE maxima around 948 Hz. These results suggest that MOC activation plays a role in selective listening.

Role of the efferent medial olivocochlear system in contralateral masking and binaural interactions: an electrophysiological study in guinea pigs.

Contralateral broadband noise (BBN) elevates ipsilateral auditory thresholds (central masking) and reduces the amplitude of ipsilateral brainstem auditory evoked potentials (BAEPs). Binaural interactions are complex psychophysical phenomena, but binaural interaction components are easily extracted from BAEPs to monaural versus binaural click stimulation. However, contralateral, or binaural, acoustical stimulation is known to activate simultaneously the crossed and uncrossed medial olivocochlear (MOC) efferent systems and decrease activity in both cochleas. Particularly, contralateral BBN stimulation suppresses in part ipsilateral peripheral activity. What is the role of such contralaterally induced peripheral suppression in the overall changes in central BAEPs observed during contralateral masking or binaural stimulation? Compound action potentials (CAPs) of the auditory nerve and BAEPs were recorded simultaneously in awake guinea pigs from electrodes chronically implanted on the round window of the cochlea and the surface of the brain. Peripheral and central measures of contralateral masking and binaural interactions were obtained from responses to monaural or binaural clicks, with or without contralateral BBN, recorded before, during, and after the reversible blockade of the MOC function following a single intramuscular injection of gentamicin. Contralateral BBN effectively reduced the amplitudes of CAP and of all BAEP peaks. CAP to ipsilateral click did not, however, change significantly from monaural to binaural click stimulation; still, normal binaural interaction components developed in the BAEPs. When the medial efferent function was blocked by gentamicin, the normal contralateral BBN suppression of CAP and of the earliest BAEP peak was lost; however, the later BAEP peaks were suppressed by contralateral BBN as before gentamicin, and the central binaural interaction components were unchanged. In these experimental conditions, the MOC efferent system seems to play little role in centrally recorded contralateral masking and binaural interactions.

Acute and chronic effects of aminoglycosides on cochlear hair cells.

The first detectable effect on the auditory system after a single high-dose injection of an aminoglycosidic antibiotic (AA) like gentamicin (GM) is the reversible blockade of medial efferent function, probably via blockade of calcium channels at the base of the outer hair cells (OHC). The kinetics of this effect are compatible with that of the molecule in perilymph. In the course of chronic treatment with lower doses, however, ototoxicity develops only after several days of treatment. Still GM can be observed inside the OHCs as soon as 24 hours after the first injection, and will be still present in some OHCs as long as 11 months after a chronic, nonototoxic 6-day treatment. In vitro, the short-term viability of isolated OHCs is not affected by exposure to AAs, but their transduction channels and their response to acetylcholine are reversibly blocked. However, developing organs of Corti in culture are highly and rapidly affected by exposure to AAs. Yet during direct intracochlear perilymphatic perfusion of GM, 2-mM solutions are not ototoxic, and with perfusion with a 20-mM solution ototoxicity develops only after several days of perfusion. From these various observations one can describe some aspects of the mechanisms of ototoxicity of AAs, from their access to perilymph and endolymph, to penetration in the hair cells, likely via endocytosis at their apical pole, and intracellular cytotoxic events.

Aminoglycoside Ototoxicity and the Medial Efferent System: II. Comparison of Acute Effects of Different Antibiotics

Gentamicin (GM) has been shown to reversibly reduce the ability of contralateral noise to suppress ipsilateral cochlear activity, in a dose-dependent manner. However, during chronic administration of lower doses (60 mg/kg) the involvement of medial efferents could not be demonstrated. The purposes of the present study were to determine whether other aminoglycosides would display the same acute effects as GM and whether there was any correlation between their specificity and degree of cochlear and vestibular toxicity and their potency of blockade of the medial efferent system. Thus, we observed changes in ipsilateral ensemble background activity (EBA) of the VIIIth nerve without and with contralateral low level (55 dB SPL) broadband noise stimulation, in awake guinea pigs (GPs), before and after one single high-dose intramuscular injection of different aminoglycoside antibiotics (AAs) (gentamicin, amikacin, neomycin, netilmicin, streptomycin, tobramycin). For comparison, the effects of strychnine, a known antagonist of the efferent transmission and of cisplatin, an antineoplastic agent with cochleotoxic properties were also studied. Netilmicin displayed blocking properties similar to GM, although less pronounced, while amikacin and neomycin had no effect on medial efferent function. With tobramycin and streptomycin a decrease in suppression was usually associated with a reduction of the EBA measured without acoustic stimulation. However, with cisplatin, suppression was still effective when EBA was severely decreased. We could not observe specific effects of strychnine on medial efferent function. In conclusion, no correlation was found between specificity and degree of AA ototoxicity and their action on the medial efferent system.

Bioelectrical cochlear noise and its contralateral suppression: relation to background activity of the eighth nerve and effects of sedation and anesthesia.

The bioelectrical activity of the cochlea, without any ipsilateral acoustic stimulation, was recorded in awake guinea pigs (GPs) between electrodes chronically implanted at the round window (RW) and the skull. Measuring its power in the band centered around 1.0 kHz (0.5-2.5 kHz) provided an indirect measure of the ensemble background (EBA) activity of the eighth nerve. Contralateral white-noise (CLWN) stimulation reduced this EBA, presumably by activation of medial olivocochlear fibers. The aim of the investigation was to validate measurements of EBA and of its contralateral suppression in order to study the medial efferent function. The first goal was to find the best conditions for recording the EBA in the absence of ipsilateral stimulation and for studying its suppression by contralateral acoustic stimulation, which implies that no noise was generated by the experimental animal. Thus recordings were compared in normal, awake GPs and in GPs under sedation with xylazine, anesthetized with a combination of xylazine and ketamine, and with and without temperature regulation. In order to monitor the effects of sedation and anesthesia, the recordings were analyzed not only in the 0.5- to 2.5-kHz frequency band but also in the other frequency bands, 5-50 Hz, 50-150 Hz, and 150-500 Hz, which presumably include general central and neuromuscular contributions. The results show that sedation with xylazine accompanied by regulation of body temperature does not affect the EBA value nor its contralateral suppression. Nevertheless, anesthesia should be avoided, even with control of body temperature. The second goal of this study was to identify the specific cochlear contribution to the raw RW signal. Thus recordings were performed in normal and deafened animals and analyzed in the frequency band 0.5-2.5 kHz and also in the other frequency bands of 5-50 Hz, 50-150 Hz, and 150-500 Hz. The results indicate that most of the cochlear activity lies in the frequency band 0.5-2.5 kHz, with also some minor contribution coming from the 150- to 500-Hz band. Analysis and comparison of power values in the different conditions indicate that specific cochlear EBA power was about 60 microV2. From a commonly accepted mean background discharge rate of 50 spikes/s (sp/s), the EBA power without CLWN should have been around 4.4 microV2 if the fibers' activity was random. This difference suggests that there is probably some degree of synchrony between individual fibers. There was a reduction of approximately 45% during CLWN stimulation. This suppression might correspond to a reduction in both discharge rate and synchrony of the fibers.

Rapid, reversible elimination of medial olivocochlear efferent function following single injections of gentamicin in the guinea pig

Measurements were made of the ability of nonsimultaneous, contralaterally presented broadband noise maskers to suppress ipsilaterally-evoked compound action potentials (CAPs) of the auditory nerve to 8-kHz tone pips in guinea pigs. Contralateral acoustic stimuli have been shown to suppress responses to ipsilateral stimuli through the action of the medial olivocochlear efferent bundle. In this study, maximum suppression across subjects ranged from 2–6 dB. The ability of the contralateral noise to suppress ipsilateral CAPs was rapidly reduced beginning within minutes of a single intramuscular injection of the aminoglycoside antibiotic gentamicin (150 mg/kg), and, in general, was completely abolished by 1.5–2 h. Changes in suppression were presumably produced by gentamicin-induced blockade of presynaptic calcium channels on the medial olivocochlear efferents and the absence of any measurable change in either CAP thresholds to different to frequencies or CAP input/output. Suppression was partially restored in some animals after 24 h, and was fully recovered in all subjects within 96 h postinjection. The present studies suggest that measures of efferent function might form the rational basis for an objective means to assess aminoglycoside insult on the cochlea in the absence of hair cell damage. These results also indicate that single injections of gentamicin offer a reversible, non-invasive model in which medial efferent function can be studied in behavioral animals.