Spencer B. Smith
Au.D./Ph.D. student at the University of Arizona
*Please note: This article is Part II of a two-part series. Please refer to last month’s featured article to review Part I.
Part I of this series briefly reviewed the anatomy and physiology of the mammalian caudal efferent auditory system and presented some animal research suggesting its putative role in auditory processing. In Part II, experiments on the human caudal efferent system will be reviewed and a discussion regarding the progress and limitations of clinical assays of the caudal efferent system will be presented.
Human Experiments –
With the advent of otoacoustic emission (OAE) analyzer systems, it became possible to non-invasively study the function of the caudal efferent system in the human cochlea. OAEs are acoustic waveforms recorded in the ear canal that are presumably related to outer hair cell electromotility, and thus are sensitive to changes in outer hair cell function induced by the MOC system (Guinan, 2006). The most common MOC reflex assay reported in humans is the contralateral suppression (or “inhibition”; Guinan, 2010) of OAEs technique. In this technique OAEs are recorded first in quiet and then with noise presented to the opposite ear, which activates a portion (specifically uncrossed MOC fibers) of the MOC reflex. The amplitude and phase differences between OAEs recorded in quiet and with contralateral noise are used to quantify attenuation of the cochlear amplifier mediated by the MOC reflex. The amount of OAE suppression with MOC activation typically ranges from 1-4 dB overall in normal hearing listeners and is most evident in the cochlear tonotopic frequency range of 1-4 kHz (Berlin et al., 1993a). Various types of contralateral noise have been employed to elicit the MOC reflex, including continuous or pulsed broadband and narrowband noise, speech babble, as well as steady-state and amplitude-modulated tones (Berlin et al, 1993a; Maison et al, 1997, 1999; Smith et al, 2001). In general, broadband noise is a more effective suppressor than narrowband noise or tones (Berlin et al, 1993a; Norman & Thornton, 1993). Suppressors can be presented in a steady-state fashion throughout OAE recording (Hood et al, 1996) or in trials with short duration CAS temporally preceding the evoking stimulus (Berlin et al, 1995). Although binaural noise has been used to elicit crossed and uncrossed MOC fibers and thus maximize the suppressive effect of the MOC reflex, this measurement is technically more time consuming and difficult to execute because the binaural noise must temporally precede the OAE elicitor.
A major limitation of human OAE suppression measurements is that they do not directly demonstrate how the MOC reflex shapes the neural output of the inner ear. Few studies have examined the effect of contralateral noise on auditory nerve compound action potentials in humans (Chabert et al., 2002; Folsom & Owsley, 1987; Kawase and Takasaka, 1995; Lichtenhan et al., 2015). Lichtenhan and colleagues (2015) have arguably been the most rigorous in their data collection procedures and reported that individual MOC-induced reductions in human compound action potentials are on average slightly larger than OAE suppression, on the order of 2-3 dB. This finding is in agreement with animal work indicating that OAE suppression likely underestimates the amount of neural suppression, which may be due to the combined suppressive effects of MOC and LOC systems on the neural responses (Puria et al., 1996).
Several putative roles of the human caudal efferent system have been proposed based on empirical evidence. Additionally, evaluation of efferent function in certain disordered populations has yielded atypical results, which may be clinically useful.
Improving the Neural Encoding of Speech-in-Noise:
There has only been one study describing auditory nerve “unmasking” of simple stimuli with activation of the MOC reflex in humans (Kawase & Takasaka, 1995). The authors of this study hypothesized that, as in animal models, the caudal efferent system improves the neural encoding of signals in noise. More commonly, positive correlations between the magnitude of contralateral OAE suppression and signal- and speech-in-noise perception ability have been reported (Abdala et al., 2013; Giraud et al., 1997; Kumar & Vanaja, 2004; Micheyl et al., 1995; Yilmaz et al., 2007). These studies suggest that the caudal efferent system is involved in speech-in-noise processing or, at the very least, is indicative of the overall strength of the efferent system. Importantly, some studies have shown no correlation between the two measurements (Scharf et al., 1997; Wagner et al., 2008). Abdala and colleagues (2014) reported that the strength of the MOC reflex begins to decrease in middle age, which may be related to poorer speech perception abilities in the elderly.
Evaluation of Disordered Populations:
Activation of the caudal efferent system is dependent upon proper function of afferent (inner hair cells, auditory nerve fibers, cochlear and superior olivary nuclei) and efferent (LOC/MOC fibers and outer hair cells) components of the reflex loop. Patients with auditory neuropathy and multiple sclerosis affecting the auditory brainstem do not demonstrate OAE suppression due to poor neural synchrony in this circuit (Berlin et al., 1993b; Coelho et al., 2007). Patients with myasthenia gravis, a muscular disorder affecting the synaptic release of acetylcholine, also show reduced OAE suppression, as acetylcholine is the neurotransmitter released by MOC fibers onto the base of outer hair cells; interestingly, OAE suppression strength increases with treatment of myasthenia gravis (Paludetti et al., 2001). Ototoxicity and diabetic hyperglycemia, both of which alter the metabolism of outer hair cells, can also be monitored with OAE suppression (Jacobs et al., 2012; Riga et al., 2007).
Individuals with more global deficits have demonstrated aberrant OAE suppression. Children with selective mutism, learning disabilities, and auditory processing disorder demonstrate reduced OAE suppression versus normal controls (Bar-Haim et al., 2004; Garinis et al., 2008; Muchnik et al., 2004). Tinnitus patients with hyperacusis but otherwise normal hearing demonstrate “hyperactive” MOC activity (Knudson et al., 2014), and those with autism have reportedly shown both a lack of OAE suppression (Danesh & Kaf, 2011) as well as hyperactivity (Wilson et al., 2015). The discrepancy in these results is perhaps due to the fact that some studies have failed to sort autistic participants into hyperacusic and non-hyperacusic groups. It should be noted that methodology differs widely in this body of literature, making it difficult to compare results across studies (Mishra, 2014). Thus, while the results of these studies are scientifically interesting, they by no means have clinical diagnostic value for the abovementioned disorders.
Predicting Noise-Induced Hearing Loss and Benefit of Auditory Training:
In two large longitudinal studies, Lapsley-Miller and colleagues (2006, 2009) reported an average reduction in OAE amplitudes in military servicemen exposed to noise, even though group hearing thresholds remained stable on average. Individuals with lower baseline OAE amplitudes were six- to nine-times more likely to develop permanent threshold shifts, indicating that OAEs may be a predictor of noise-induced hearing loss susceptibility. In the future, individuals with lower baseline OAE measurements may be good candidates for prophylactic pharmaceutical treatments to prevent noise induced hearing loss.
The neuroplastic effects of auditory training may, in part, be facilitated by the caudal efferent auditory system. For example, it is not unreasonable to assume that speech-in-noise training bolsters the anti-masking effect of the caudal efferent system and thus improves listening in noise. de Boer and Thornton (2008) reported that weaker baseline MOC reflex strength was associated with greater training-induced improvement on a speech-in-noise perception task. Further, MOC reflex strength increased in individuals demonstrating a significant improvement on the speech-in-noise task after training. These measurements may be useful in identifying which patients would be most likely to benefit from auditory training and would provide an objective means of quantifying training-based neuroplasticity.
Top-down Control of Cochlear Processes During Active Listening:
The effects of attention on cochlear function have been non-invasively studied in humans using OAE measurements. Because the efferent system enters the inner ear as part of the vestibular branch of the eighth nerve, patients with normal hearing who have undergone vestibular neurectomy for intractable vertigo provide unique opportunities to study the proposed top-down effects of the efferent system on various auditory abilities. In several studies on vestibular neurectomy patients, Scharf and colleagues (1994, 1997) tested many auditory abilities pre- and post-surgery including frequency and intensity discrimination of tones, detection of masked tones, and loudness adaptation. None of these measures significantly differed between pre- and post-surgery, calling into question the functional role of the caudal efferent system, at least for perception of simple stimuli. They did find, however, that unexpected off-frequency tones were more easily detected after neurectomy, indicating that the efferent system may actively suppress non-relevant frequency channels during active listening. Many other studies have indicated that OAEs are altered during attention, suggesting top-down modulation of cochlear function (Avan & Bonfils, 1992; de Boer & Thornton, 2007; Ferber-Mart et al., 1995; Froehlich et al., 1990; Garinis et al., 2011; Harkrider & Bowers, 2009; Maison et al., 2001; Perrot et al., 2006; Puel et al., 1988; Smith & Cone, 2015).
Clinical Tests of the Caudal Efferent Auditory System:
As demonstrated in the overview presented above, tests such as OAE suppression can provide useful information about the integrity of the caudal efferent system and the functional abilities of a listener. Why, then, are these tests not being implemented clinically? The sections that follow describe some outstanding issues with assays of caudal efferent system function with a specific focus on OAE suppression measurements.
Confusion Regarding the “Best” Type of OAE for MOC Reflex Measurements:
In the clinic, we have traditionally classified OAEs by the type of evoking stimulus used. For example, when two tones are presented to the ear and OAE measurements are made at frequencies mathematically related to those tones, we call the measurement a distortion product OAE (DPOAE). When a click or tone burst is used to evoke an emission, we call this a transient evoked OAE (TEOAE). Stimulus frequency OAEs (SFOAEs) are evoked with a simple pure tone and spontaneous OAEs are present in the absence of an evoking stimulus. Earlier work on MOC reflex suppression using different “types” of OAEs yielded apparent discrepancies in MOC reflex strength. For example, some studies reported that DPOAEs could be suppressed or enhanced by ~10 dB or more with activation of the MOC reflex (e.g., Muller et al., 2005), whereas TEOAE suppression is generally far less. This led to the misconception that one type of OAE is more suitable for MOC reflex measurements than another. However, when we conceptualize and classify OAEs not by their evoking stimuli but by the generation mechanisms underlying each “type” of OAE, these apparent discrepancies are better understood. For example, we now understand that DPOAEs are comprised of energy from at least two different cochlear “sources” (reflection and distortion) and both sources are differentially impacted by activation of the MOC reflex (Abdala et al., 2009). Depending on how emission energy from these two sources combine in the ear canal, DPOAEs may appear to be suppressed, enhanced, or unchanged with MOC reflex activation. Conversely, TEOAEs are comprised of energy only from cochlear reflection sources. While we now understand the mechanistic differences underlying discrepancies in suppression of each “type” of emission, the best OAE for MOC reflex measurement is not currently clear.
An alternative to measuring efferent effects on OAEs would be to measure suppression of compound action potentials. This could be accomplished with an electrocochleography electrode and headphones to deliver the evoking (ipsilateral) stimulus and broadband (contralateral) suppression noise. An advantage to this approach would be that factors influencing OAE recordings (e.g., hypermobile tympanic membrane, tympanosclerosis, etc.) could be circumvented while still assaying the effect of the efferent system on the neural output of the cochlea. However, as Lichtenhan et al. (2015) concede, the immense averaging required to separate a “true” efferent induced attenuation of compound action potential amplitude from recording variability makes this test infeasible for clinical use.
Test Retest Reliability and Stability of MOC Reflex Measurements are Poorly Understood:
As mentioned previously, the size of MOC effects on OAEs is quite small, on the order of 1-4 dB. While this is not a problem per se, the variability and test-retest reliability of MOC reflex measurements must be understood for clinicians to be confident that they are observing “true” changes and not random fluctuation in emission amplitude. Few studies have demonstrated the variability and test-retest reliability of OAE suppression. While some authors have found MOC reflex variability to be quite small and stable over short intervals (< 2 weeks; Kumar et al. 2013; Mishra & Lutman 2013; Marshall et al. 2014) others have concluded that longer-term variability is too large for OAE suppression measurements to be used in the clinic (Mertes & Goodman, 2016).
“All-in-one” commercial OAE analyzers with MOC reflex modules and built-in contralateral noise generators have only recently been developed. In order for MOC reflex measurements to be broadly applied in the clinic, it is recommended that stimulus and contralateral noise bandwidths and levels are standardized across clinical protocols. Furthermore, the newest systems do not have built-in contralateral acoustic reflex threshold measurement routines, which are prerequisite to OAE suppression measurements to ensure that OAE amplitude reduction is purely due to cochlear and not middle ear mechanisms. It is also unclear whether quantifying OAE suppression in terms of raw dB attenuation or as a normalized percentage value leads to more stable recordings.
In summary, the human caudal efferent auditory system is believed to be an important mechanism involved in early level auditory processing. Assessment of this portion of the auditory system may allow clinicians to provide a more detailed diagnostic picture for their patients and determine which clients are at higher risk for noise-induced hearing loss or are appropriate candidates for auditory training. Several technical and theoretical issues must be addressed before clinical assays of caudal efferent system function are widely adopted; however, there has been great progress on this front recently.
Spencer B. Smith is an Au.D./Ph.D. candidate at the University of Arizona. His research examines the role of the human caudal efferent auditory system in the neural encoding of simple and complex stimuli in noisy environments. To support his research, Spencer has been awarded grants and scholarships from the National Institutes of Health (F30), the American Academy of Audiology Foundation, the American Speech-Language-Hearing Foundation, and the University of Arizona.
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