**2.1 Auditory evoked potentials**

26 Hearing Loss

\*(Allen, 1986; A. Davis et al., 1997; Kral & O'Donoghue, 2010; Marschark & Wauters, 2008; Schroeder

The widespread use of universal neonatal hearing screening has been established based on the growing body of evidence that early detection of hearing loss leads to early aural rehabilitation (Kennedy, McCann, Campbell, Kimm, & Thornton, 2005). Multiple studies have demonstrated the deleterious effect of bilateral hearing loss on speech and language development (Allen, 1986; A. Davis et al., 1997; Thompson et al., 2001; Wake, Hughes, Poulakis, Collins, & Rickards, 2004b). However if caught early, the effects of hearing loss are somewhat mitigated. Yoshinaga-Itano *et al.* reported on the ability of early detection of hearing loss to improve language development as measured by standardized testing (Yoshinaga-Itano, Sedey, Coulter, & Mehl, 1998; Yoshinaga-Itano, 2003). Children enrolled into language programs at earlier ages have improved vocabulary and verbal reasoning skills on standardized tests at 5 years of age (Moeller, 2000) Opponents to Universal screening cite the great cost of such widespread screening as well as efficacy in earlier years. From a pragmatic, fiduciary perspective, a cost-effectiveness study has shown that as a result of special education needs, failure to detect severe-to-profound hearing loss can cost the educational system approximately \$38 000 – 240 000 (USD) per child over their educational lifetime (Mohr et al., 2000). It would seem then that detecting these children would offset a significant amount of the cost. Furthermore, in areas that have adapted a Universal Newborn Hearing protocol, detection of congenital hearing loss has nearly

It is clear that the early detection of hearing loss has strong developmental, psychosocial and societal implications as well. Therefore, in 2007 the American Academy of Pediatrics' Joint Committee on Infant hearing endorsed the early detection of hearing loss with an aim at early intervention to improve linguistic competence and literary development (Busa et al., 2007). They recommended that all infants should be screened prior to 1 month of age. Children identified with hearing loss by screening should have a comprehensive audiological assessment by 3 months of age. After audiological assessment, children with confirmed hearing loss should receive appropriate intervention by dedicated hearing loss health care and education professionals not later than 6 months of age. Children with risk factors for hearing loss (a summary of commonly cited risk factors can be found in Table 2.) should be followed by on-going surveillance starting at 2 months of age. Unfortunately in many centers the "lost to follow up" rates approach 40% of infants who do not pass their infant screening (Choo & Meinzen-Derr, 2010). All centers must work diligently to ensure children who fail their hearing screen are referred appropriately to maximize their potential and mitigate the lifelong effects of hearing loss. The following sections will provide an

et al., 2006; Thompson et al., 2001; Wake, Hughes, Poulakis, Collins, & Rickards, 2004a)

Table 1. Detrimental Effects of Profound Hearing Loss in Childhood\*

doubled since its introduction (Choo & Meinzen-Derr, 2010).

**Speech and language development** 

**Comprised employment opportunities in later life** 

**Social-emotional development Childhood behavioral problems** 

**Self-perceived health status**

**Academic achievement** 

Measurement of auditory evoked potentials (AEP) has been possible since the 1960s. AEPs represent electrical activity occurring along the length of the auditory pathway. They are typically described by their latency from the onset of the auditory stimulus: early (0 to 15 milliseconds), middle (15 to 100 milliseconds) and late (100 to 500 milliseconds). Auditory brainstem responses (ABR) appear to be the most clinically useful early latency AEPs for detecting hearing loss in newborns and infants ( Hecox 1974). Hecox *et al.* first speculated on the use of Auditory Brainstem Responses (ABR) as an objective method of assessing infant hearing in 1974 (Hecox & Galambos, 1974). Measurement of ABR makes use of the summation of action potentials from the cochlear nerve to the inferior colliculus of the midbrain in response to a click stimulus applied to the test ear. Since that time the use of ABR has become a widely accepted method to assess auditory function and hearing sensitivity. The commonly cited advantages and disadvantages of ABR are summarized in Table 3.

Contralateral Suppression of Otoacoustic Emissions:

and initiation of aural rehabilitation.

Simple administration – minimal training required

Results are immediately

Assess greater extent of auditory system

Requires no interpretation by

ABR results are less affected by middle ear or external ear

Average screening time is less

available

than ABR

the screener

available

debris than OAEs

Results are immediately

May detect neural or central auditory pathologies

Table 3. Advantages and Disadvantages of Existing Hearing screening methods

Otoacoustic Emissions

**Automated auditory brainstem response** 

Working Towards a Simple Objective Frequency Specific Test for Hearing Screening 29

65 and 55 dBL SPL respectively are commonly used. Responses are usually the most robust when recorded at the frequency 2f1-f2. Transient OAE testing applies a brief click to the test ear to elicit the hair cell response. As such, Transient OAE measurement lacks frequency specificity (Jacobson & Jacobson, 2004). Conversely, stimulus tones used in DPOAE testing combine frequency stimuli in a predictable way that can measure specific regions of the cochlea allowing frequency specific testing (Jacobson & Jacobson, 2004). While OAEs have been widely adapted for newborn hearing screening programs, they are still only surrogate markers for hearing. Their presence indicates normal function of the outer hair cell, middle ear and ear canal. As such, conditions such as auditory neuropathy, cochlear nerve hypoplasia or inner hair cell anomalies can be missed and may lead to delay in diagnosis

**Advantage Disadvantage** 

Cost-effective Debris or fluid in the external ear

Requires quiet environment

Only asses outer hair cell function

Failure rates are high during first

No use in fluid filled middle ear

Sensitivity – may fail to detect infants with very mild hearing loss or central auditory

Requires more operator knowledge than ABR

ABR may be susceptible to electrical interference

Sensitivity – may fail to detect Infants with very mild hearing

Requires long period of time

May take longer in noisy

Patient must be sleeping

Potential for electrical and noise

may affect results

24 hours after birth

pathologies

loss

Cost

environment

artifact

Screening ABR utilizes a click or tone pip stimulus presented via a headphone or a transducer inserted into the subject's ear. Click stimuli are commonly used and make use of a broad range of frequencies (1 – 6 kHz) but do not provide information about hearing in lower frequencies (Jacobson & Jacobson, 2004) . If necessary, tone pips can be used to acquire frequency specific information (Jacobson & Jacobson, 2004). The subject is prepared with three surface electrodes placed on the forehead and both mastoids or earlobes. The electrodes detect click or tone pip-induced action potentials that are generated in the cochlea. The signal is transmitted from along the cochlear nerve from the cochlear nucleus to the inferior colliculus. The amplitude of the action potential is measured in microvolts and averaged. The averaged potential is then plotted against time to create a waveform with characteristic peaks labeled I-VII (Table 4). Only waves I and II correspond to true action potentials. Waves III-VII are thought to represent post-synaptic activity in the major brainstem auditory centres. Given the necessity of electrode placement and duration of approximately 15 minutes, sedation is often required (Kral & O'Donoghue, 2010). The morphology and latency of the wave form is compared to a normal wave form and a pass or fail result is generated. The sensitivity of ABR is generally quoted as 84-100% and the specificity is 99.7% (A. Davis et al., 1997; Hall, Smith, & Popelka, 2004; Llanes & Chiong, 2004).

#### **2.2 Otoacoustic emissions**

Initially hypothesized in 1948 by the theoretical physicist Thomas Gold and later confirmed by Kemp in 1978, Otoacoustic emissions (OAE) now provide an important non-invasive method of auditory testing (Gold, 1948; Kemp, 1978b). OAEs are acoustic signals generated by the activity of the outer hair cells of the cochlea that occur during normal hearing. Control of outer hair cell activity is intimately linked with the olivocochlear pathway and will be discussed further in later sections. In brief, the mechanical energy generated by the outer hair cells propagates backward to the tympanic membrane. Movements of the tympanic membrane in turn produce acoustic signals that can be detected by an extremely sensitive microphone placed in the external ear canal. The presence of OAEs demonstrates the presence of functional outer hair cells suggesting the presence of a cochlea which forms the basis of this screening method. Testing of OAEs is simple and efficient requiring approximately 10 minutes. Sensitivity and specificity of OAE testing for hearing impairment ranges from 76.9-98% and 90% respectively (A. Davis et al., 1997; Llanes & Chiong, 2004; Thompson et al., 2001).

Different types of OAE can be detected but only some are useful in hearing testing (Saurini, Nola, & Lendvai, 2004). Spontaneous OAEs are obtained without any acoustic simulation. They are narrow band signals present in 40-70% of normal ears. Evoked OAEs are stimulated by acoustic signals and comprise a range of subtypes. Sustained frequency OAEs are obtained by continuous acoustic stimuli and are found in approximately 94% of people. Their measurement is typically complex and is not used very often. Transient OAEs are stimulated by clicks or tone bursts. Distortion Product OAEs (DPOAE) are produced in response to the simultaneous presentation of two stimuli and can be found in up to 98% of normal hearing individuals. As suggested by the name, stimuli for DPOAE consist of the combination of two stimuli that vary by frequency (f1 and f2) and intensity (L1 and L2). Varying the relationship of f1 and f2 and L1 and L2 determine the frequency response. Achieving an optimal response is usually obtained by setting L1 equal or greater than L2 e.g.

Screening ABR utilizes a click or tone pip stimulus presented via a headphone or a transducer inserted into the subject's ear. Click stimuli are commonly used and make use of a broad range of frequencies (1 – 6 kHz) but do not provide information about hearing in lower frequencies (Jacobson & Jacobson, 2004) . If necessary, tone pips can be used to acquire frequency specific information (Jacobson & Jacobson, 2004). The subject is prepared with three surface electrodes placed on the forehead and both mastoids or earlobes. The electrodes detect click or tone pip-induced action potentials that are generated in the cochlea. The signal is transmitted from along the cochlear nerve from the cochlear nucleus to the inferior colliculus. The amplitude of the action potential is measured in microvolts and averaged. The averaged potential is then plotted against time to create a waveform with characteristic peaks labeled I-VII (Table 4). Only waves I and II correspond to true action potentials. Waves III-VII are thought to represent post-synaptic activity in the major brainstem auditory centres. Given the necessity of electrode placement and duration of approximately 15 minutes, sedation is often required (Kral & O'Donoghue, 2010). The morphology and latency of the wave form is compared to a normal wave form and a pass or fail result is generated. The sensitivity of ABR is generally quoted as 84-100% and the specificity is 99.7% (A. Davis et al., 1997; Hall, Smith, & Popelka, 2004; Llanes & Chiong, 2004).

Initially hypothesized in 1948 by the theoretical physicist Thomas Gold and later confirmed by Kemp in 1978, Otoacoustic emissions (OAE) now provide an important non-invasive method of auditory testing (Gold, 1948; Kemp, 1978b). OAEs are acoustic signals generated by the activity of the outer hair cells of the cochlea that occur during normal hearing. Control of outer hair cell activity is intimately linked with the olivocochlear pathway and will be discussed further in later sections. In brief, the mechanical energy generated by the outer hair cells propagates backward to the tympanic membrane. Movements of the tympanic membrane in turn produce acoustic signals that can be detected by an extremely sensitive microphone placed in the external ear canal. The presence of OAEs demonstrates the presence of functional outer hair cells suggesting the presence of a cochlea which forms the basis of this screening method. Testing of OAEs is simple and efficient requiring approximately 10 minutes. Sensitivity and specificity of OAE testing for hearing impairment ranges from 76.9-98% and 90% respectively (A. Davis et al., 1997; Llanes & Chiong, 2004;

Different types of OAE can be detected but only some are useful in hearing testing (Saurini, Nola, & Lendvai, 2004). Spontaneous OAEs are obtained without any acoustic simulation. They are narrow band signals present in 40-70% of normal ears. Evoked OAEs are stimulated by acoustic signals and comprise a range of subtypes. Sustained frequency OAEs are obtained by continuous acoustic stimuli and are found in approximately 94% of people. Their measurement is typically complex and is not used very often. Transient OAEs are stimulated by clicks or tone bursts. Distortion Product OAEs (DPOAE) are produced in response to the simultaneous presentation of two stimuli and can be found in up to 98% of normal hearing individuals. As suggested by the name, stimuli for DPOAE consist of the combination of two stimuli that vary by frequency (f1 and f2) and intensity (L1 and L2). Varying the relationship of f1 and f2 and L1 and L2 determine the frequency response. Achieving an optimal response is usually obtained by setting L1 equal or greater than L2 e.g.

**2.2 Otoacoustic emissions** 

Thompson et al., 2001).

65 and 55 dBL SPL respectively are commonly used. Responses are usually the most robust when recorded at the frequency 2f1-f2. Transient OAE testing applies a brief click to the test ear to elicit the hair cell response. As such, Transient OAE measurement lacks frequency specificity (Jacobson & Jacobson, 2004). Conversely, stimulus tones used in DPOAE testing combine frequency stimuli in a predictable way that can measure specific regions of the cochlea allowing frequency specific testing (Jacobson & Jacobson, 2004). While OAEs have been widely adapted for newborn hearing screening programs, they are still only surrogate markers for hearing. Their presence indicates normal function of the outer hair cell, middle ear and ear canal. As such, conditions such as auditory neuropathy, cochlear nerve hypoplasia or inner hair cell anomalies can be missed and may lead to delay in diagnosis and initiation of aural rehabilitation.


Table 3. Advantages and Disadvantages of Existing Hearing screening methods

Contralateral Suppression of Otoacoustic Emissions:

**4. The olivocochlear pathway 4.1 Neuroanatomy and physiology** 

2000b).

make up this spectrum may allow patients to be treated earlier.

Working Towards a Simple Objective Frequency Specific Test for Hearing Screening 31

improvement (Attias & Raveh, 2007; Rance & Barker, 2008b). As such determination of patient who will benefit from hearing aids or cochlear implantation is difficult (Raveh, Buller, Badrana, & Attias, 2007). The development of improved testing techniques that can be used to diagnose, characterize, and differentiate between the numerous diseases that

Cochlear function including the sensitivity and frequency tuning of the peripheral auditory system is influenced by incoming acoustic stimuli but also higher cochlear function. The olivocochlear pathway is a neural pathway which innervates cochlear outer hair cells (OHC), linking the superior olivary complex to the cochlea. Further insights into this pathway may improve our ability to screen for various forms of hearing loss such as ANSD. The olivocochlear neural pathway is comprised of efferent neurons that travel from the superior olivary complex in the brainstem to cochlear hair cells. First described in 1946, Rasmussen (Rasmussen, 1946) traced the neural fibres from the floor of the fourth ventricle, along the inferior and superior vestibular nerves, then into the cochlear nerve in the bundle of Oort (the vestibulocochlear anastomosis). Later he confirmed passage of the pathway into the cochlea and named it the olivocochlear bundle (Rasmussen, 1953). This neural pathway, the olivocochlear efferent pathway, is now thought to play an important role in the olivocochlear reflex. There appear to be two forms of olivocochlear efferent fibres, medial olivocochlear (MOC) and lateral olivocochlear (LOC) efferents. The majority are the thin, unmyelinated fibres of the LOC system arising from the lateral superior olive and travel via the vestibular nerve to the cochlea where they innervate the auditory nerve supplying the inner hair cells (Kimura & Wersäll, 1962; Warr, 1975). While the LOC system received contributions from both sides of the brainstem, the majority of fibres innervate the ipsilateral cochlea (Guinan Jr, 2006). Thick, myelinated neurons of the MOC pathway originate in the medial part of the superior olivary complex. A portion of fibres cross the midline to the contralateral cochlea while others project to the ipsilateral cochlea both via the vestibular nerves (Guinan Jr, 2006). Within the cochlea the MOC fibres innervate the outer hair cells; this is referred to as the medial olivocochlear system (MOCS). The MOCS is innervated by ascending and descending neural pathways. Descending innervations arises from the inferior colliculus and auditory cortex (Mulders & Robertson, 2000a; Mulders & Robertson,

Ascending innervation arises predominantly from the contralateral cochlea, by way of interneurons which cross the brainstem from cochlear nucleus to the olivary complex (Brown, Venecia, & Guinan, 2003; Morest, 1973; Ye, Machado, & Kim, 2000). The majority of MOCS fibres cross back over the midline to innervate the cochlea from which innervation is received (Azeredo et al., 1999; M. Liberman & Brown, 1986). A smaller proportion of MOCS fibers do not travel back across the brainstem and therefore innervate the cochlea on the same side. As they are stimulated by signals from the contralateral ear they provide a mechanism by which stimulation of one ear can influence the detection of acoustic signals

by the other ear (Azeredo et al., 1999; Warren III & Liberman, 1989a).


Table 4. Characteristic auditory brainstem response waves
