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E. Kösemihal et al.
b
Fig. 8.3 (a) An example of a TEOAE result screen. The red column shows the signal, and the gray column shows the noise. The SNR, shown by the green line,
provides information about the test under appropriate conditions. (b) An example of a DPOAE result screen. SNR is indicated by the red line
8 Behavioral andElectrophysiological Tests inAudiology
Table 8.6 TEOAE test results and interpretation
TEOAE results Present No answer “Inconclusive” or “not clear (NC)” Amplitudes between
10 and+30dB SPL
TE-NFa (SNR) 6dB SPL
a
NF Noise oor
Table 8.7 DPOAE results and interpretation
DPOAE amplitude (dB SPL) Within normal
Signal-to-noise ratio (SNR)=Distortion productNoise oor (dB)
Low noise level (LNL) Ideally
At low noise levels (5dB SPL)
SNR 5dB SPL
DPOAE results Present and
normal
limits (>0dB SPL)
6dB 6dB
<10dB SPL
Recording conditions are not sufcient (e.g., noisy environment or probe placement problem)
Possibly present but abnormal Absent
Below normal limits (e.g., <5% of normal and<0dB SPL)
Ideally <10dB SPL
149
Below noise oor
<6dB
Ideally <10dB SPL
8.5.3 Auditory Evoked Potentials
Auditory evoked potentials (AEPs) are waveforms that are generated by synchro­nized neural activity in the central auditory nervous system in response to acous­tic stimuli. They can reect electrophysiological function at different levels in the auditory system. Because AEPs objectively assess the integrity and function of the peripheral and central auditory systems, they have become a powerful tool for determining hearing thresholds in children who are too young to undergo audiometric testing and others who are unable to comply with behavioral test­ing [54].
AEPs are widely used for purposes such as estimating hearing thresholds, evalu­ating central auditory nervous system function, newborn hearing screening, and monitoring auditory nervous system function during surgery [55].
It is possible to categorize AEPs based on the region in the central auditory ner­vous system from which they are obtained and the latency interval during which the response occurs (Fig.8.4).
Although there are several methods for grouping AEPs in audiological evalua­tions, the most commonly used method is to classify them according to the latency intervals in which they are obtained:
• Electrocochleography (ECochG): This occurs within the rst 5ms after the sig-
nal presentation. It reects activity of the cochlea and CN VIII.
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Fig. 8.4 Family of auditory evoked potentials
E. Kösemihal et al.
• Auditory brainstem response (ABR): This occurs within 1–10 milliseconds (ms).
This is the most commonly used AEP.The ABR reects neural activity in CN
VIII and the brainstem.
• Middle latency response (MLR): This occurs within 10–50ms. The MLR wave-
form mainly reects activity in the midbrain, thalamocortical projections, and
primary auditory cortex.
• Late latency response (LLR): This occurs within 50–250ms (or later in infants).
It reects activity in the primary auditory regions of the cerebral cortex and
related structures.
• Auditory steady-state response (ASSR): The ASSR is evoked by a periodic stim-
ulus and reects phase-locked steady-state neural activity in response to an
ongoing stimulus. The ASSR is recorded in the frequency domain so that peri-
odic activity can be extracted. This differs from the transient evoked responses
(ECochG, ABR, MLR, LLR), which are usually analyzed by examining the
waveform in the time domain. The generators of the ASSR depend on the modu-
lation rate of the stimulus; responses to slow rates originate from more central
brain structures. In contrast, responses to high rates originate from the more
peripheral auditory nerve and brainstem structures [56].
8.5.3.1 Auditory Evoked Response Measurement Principles
andTechniques
Most clinically used auditory evoked responses (AERs) reect electrical brain responses that are at lower voltages than responses obtained from other activities in the brain and body (e.g., electroencephalography (EEG) and cardiac and muscle activity). Therefore, unique techniques and equipment are used to measure and iso­late the actual AERs from other sources of electrical “noise.” Although the measure­ment principles for AERs are the same, the recording parameters for each differ. All AERs are typically recorded with electrodes placed on the scalp that collect electrical voltages generated in the brain. The names of these electrode sites are standardized according to the international 10–20 electrode system. In clinical practice, a three- or four-electrode array is commonly used for single- and two-channel recordings. However, a 32- or 64-electrode array with a unique cap is also used in neurological examinations and experimental studies. In the most common electrode placement, the non-inverting electrode (an active or positive electrode) is placed at the center of
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the forehead toward the hairline (Fz) or at the vertex at the top of the head (Cz). The inverting electrode (a reference or negative electrode) is placed on the right and/or left earlobes (A1, A2) or on the mastoid bone (M1, M2). The ground electrode (a neutral or common electrode) is placed on the forehead or root of the nose (Fpz).
Recording electrodes detect the minimal electrical voltages reecting activation of the central auditory nervous system in response to repeated auditory stimuli and transmit this information to a preamplier where the responses are amplied. Filtering and signal averaging are performed to separate unwanted electrical activity from the time-locked auditory neural responses to the stimuli. The aim is to increase the quality and reliability of the measurement using methods such as digital ltering of the resulting waveform, artifact rejection (AR) to eliminate muscle or other elec­trical noise, noise-weighted averaging, and checking the reproducibility rate/record­ing quality using metrics provided by the AER software. In short, the AER test recording process requires well-connected, low-impedance electrodes, low-noise ampliers, ltering, response averaging, and digital signal processing. Selection of appropriate recording parameters is critical in AER measurement [56].
8.5.3.2 Auditory Evoked Brainstem Response
The auditory brainstem response (ABR), the most commonly used evoked potential, is obtained at the brainstem level. It occurs within the rst 10ms of presentation of an auditory stimulus. A typical ABR waveform consists of ve peaks separated by approximately 1ms. The ve peaks that make up the ABR waveform are labeled with Roman numerals. Waves I, III, and V are the peaks evaluated most often in clinical applications [54]. Figure8.5 shows an example of the ABR waveform for an adult with normal hearing.
The ABR test is sensitive to disorders at the level of CN VIII and the auditory brainstem [54]. It is useful in the diagnosis of vestibular schwannoma and brain­stem-level disorders. It can also be monitored during surgery to remove CN VIII tumors to preserve hearing. In addition, it is widely used as an objective test to estimate hearing thresholds in young children and for newborn hearing screening. Normal outer, middle, and inner ear function is required for a normal ABR.The latency and amplitude values of the obtained waveform are compared to normative values and provide information on the integrity and status of the auditory nervous system up to the upper brainstem [54, 55].
The ABR is used in newborn hearing screening and hearing loss diagnosis. Information obtained from ABR testing should be combined with the results of other objective measures, such as tympanometry, acoustic reexes, and OAEs, and behavioral assessment to achieve accurate and precise hearing assessment [56].
The ABR can be recorded in newborns and premature infants after birth. The latencies, amplitudes, and morphology of the waves reect developmental changes in brainstem maturation and nerve myelination during the rst 18months of life. By 24months, brainstem maturation is complete and the ABR waveform becomes sim­ilar to that of adults. In clinics, normative data appropriate for the baby’s age and months are necessary to analyze and interpret ABRs in infants younger than 18months [56].
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Fig. 8.5 (a) An example of an adult ABR waveform obtained at 80dB nHL.Waves I, III, and V are labeled. (b) The latency–intensity function. As the intensity increases, the latency is expected to decrease
Stimulus Types
Click, chirp, or tonal stimuli are used for ABRs. Recently, speech stimuli have also been used, although this is uncommon for audiometric assessment. Speech ABR has been used as a diagnostic test for central auditory processing disorder.
The click stimulus can provide general information about hearing and hence may be used for screening ABRs. The click stimulus is a broadband (100–10,000Hz) and short-duration (0.1ms or 100μs) stimulus. Because of these characteristics, a strong ABR can be elicited by synchronizing the ring of multiple auditory nerve bers [57]. The click ABR does not reect frequency-specic hearing and hence cannot be used to reliably measure hearing thresholds at different frequencies.
The chirp stimulus is created by taking into account the time delays that occur in the cochlea because different stimulus frequencies activate different cochlear regions due to the tonotopic structure (frequency mapping) of the cochlea, with low and high frequencies activating apical and basal cochlear regions, respectively. A widely used chirp stimulus is referred to in the literature as CE-Chirp, an abbreviation of the name of Claus Elberling, who developed the chirp stimulus. The time-dependent frequency
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sequence of the CE-Chirp stimulus is designed to match the frequency sensitivity of the cochlea, progressing from apical to basal. Lower frequencies are delivered rst, followed by higher frequencies. Because of the tonotopic organization, the entire cochlea is stimulated simultaneously and synchronous neural activation is achieved, optimizing ABR amplitudes. As a result, chirp responses are elicited at levels close to the hearing threshold obtained with the click stimulus but with higher amplitudes. The level-specic chirp stimulus (LS CE-Chirp) is a stimulus whose duration varies as a function of stimulation intensity [57]. Frequency-specic threshold estimation in infants is possible using chirps and tone burst stimuli. Both tone bursts and tonal CE-Chirp stimuli can be used for frequency-specic assessment, to obtain frequency­specic ABRs at 500, 1000, 2000, and 4000Hz. It is important to assess hearing across the frequency range so that the auditory conguration can be determined to support hearing aid tting for individuals who cannot complete pure-tone audiome­try. Agreement between ABR and pure-tone audiometry thresholds is achieved using appropriate equipment calibration and correction factors [58, 59].
Stimulus Polarity
Polarity refers to the direction in which the diaphragm in the headphone moves rst with the stimulus presentation. “Rarefaction” is the term used for the direction in which the pressure decreases in the ear canal, and “condensation” is used for the direction in which it increases. Many AER instruments offer alternating polarity. That is, the earphone dia­phragm moves in two directions, alternately. This is used to cancel electromagnetic stimulus artifacts, but it is also clinically important to separately examine the waveform evoked by single-polarity stimuli. For example, it is expected that the rarefaction polar­ity will be used for clicks because of the larger wave amplitudes and that the alternating polarity will be used for tonal stimuli because of their longer duration and the need to reduce stimulus-related artifacts to better observe responses to tonal stimuli. Separately examining the waveform evoked by rarefaction and condensation polarities is essential in diagnostic practice as this reveals the presence of cochlear microphonics (CMs), which is a critical nding in the diagnosis of auditory neuropathy spectrum disorders (ANSDs) [59, 60]. Because cochlear microphonics are preneural and reect cochlear hair cell activity, the polarity of the response follows the stimulus polarity. The presence of cochlear microphonics with an absent ABR is indicative of an ANSD.
Stimulus Presentation Rate
This refers to the number of stimuli delivered per second. A rate between 11/sec, 21/ sec, or 37/sec can be used. Stimulation rates of 60/sec or higher could degrade the response and hence are not recommended for hearing threshold assessment. The higher the rate, the shorter the time needed for assessment, however. A high-rate stimuli of 70–90/sec may be useful for the diagnosis of neurodegenerative diseases such as multiple sclerosis, where neural synchronization is affected [59].
Stimulus Intensity
Neural evaluation of the ABR is performed at high-stimulus intensity levels (> 70 dB nHL (decibels normalized hearing level)) where all wave components
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(waves I–V) are visible. For diagnostic evaluation, it is recommended that nor­mative values (peak latency values of waves, interpeak latencies, and amplitudes) be obtained at the same intensity level as that used in the test battery for diagnos­tic ABR.This is because, as the intensity level decreases, latencies increase and amplitudes decrease. Waves I and III may not be seen as the intensity decreases. Wave V is the most robust component that is monitored down to 20dB nHL for clinical threshold assessment. People with normal hearing are expected to have wave V at 20dB nHL, although at 500Hz, 30dB nHL is the typical “pass” level for infant hearing assessment. Elevated ABR thresholds indicate hearing loss [59, 60].
The unit of intensity level for all auditory potential tests is dB nHL.This unit is a value that reects the average hearing thresholds for the ABR stimuli of a group of individuals with normal hearing. As mentioned earlier, frequency-specic cor­rection factors adjust the thresholds obtained with tonal stimuli to those obtained with pure-tone audiometry in dB HL.Some instruments can use dB SPL for clinical testing and research purposes; however, care needs to be taken when equating these levels to audiometric thresholds [59, 60].
Analysis Time (Recording Epoch)
ABRs typically do not exceed 10 ms, even in pathological cases. Therefore, an analysis time of 12–15 ms is appropriate. If a longer analysis time is used, the waves may appear more elongated with smaller amplitudes, making it difcult to deter­mine thresholds. In very young infants with conductive hearing loss, a longer time window of 20ms may be required to identify ABR wave V and the following nega­tive peak.
Filters
In diagnostic ABR testing, unwanted physiological noise is recorded in addition to the responses generated by the auditory stimuli, but the energy of this noise is gen­erally <100Hz. A high-pass lter set at 100Hz is preferred for click ABR; however, a lower value of high-pass lter (30Hz) is optimal for frequency-specic ABR.The choice of high-pass lter should effectively reduce artifacts and unwanted noise without affecting the ABR amplitude. A low-pass lter should be selected to avoid excessive “rounding” of the waveform. The optimal low-pass lter is 2500 or 3000Hz for accurate and precise recording of peak ABR latencies. A 30–1500-Hz bandpass lter may be preferred for tonal air and bone ABR testing [59, 60].
Artifact Rejection Level
The artifact rejection (AR) level should be as low as possible to achieve a good signal-to-noise ratio in AEP testing whilst still allowing for clinically acceptable recording times. Efforts should be made to reduce muscle activity and electrical noise picked up by the electrodes. Under good recording conditions, an artifact rejection level of no more than ±10μV is suggested, but, depending on the condi­tions, a higher value (e.g., ±40μV) may be preferred. Noise-weighted averaging can also help reduce noise and improve waveform quality.
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Number ofSweeps
Under optimum conditions, 1500–2000 sweeps per waveform are usually sufcient. In cases where the residual noise level is high, more sweeps may be required. The relationship between AR level and sweeps follows a quadratic law; if the AR level is doubled to ±20μV to achieve the same residual noise, the number of sweeps must be quadrupled from 2000 to 8000 [59, 61]. However, rather than simply increasing the number of sweeps, it may be more benecial to stop the test, ensure proper condi­tions, and restart. Using a xed number of sweeps is not appropriate in all situations.
Electrodes
Disposable electrodes are gradually replacing reusable electrodes. Disposable Ag/ AgCl electrodes are available. Although disposable adhesive electrodes may resem­ble electrocardiogram (ECG) electrodes, adhesive electrodes designed for neuro­logical assessment are preferred. These electrodes are placed in regions numbered and named according to the international 10–20 system. According to this system, the ground (common) electrode is placed on the forehead, the positive (non­inverting) electrode is placed on the upper forehead (Fz) or vertex (Cz), and the negative (inverting) electrode is placed on the mastoid (M1–M2) or earlobe (A1– A2). Placement in different regions affects wave amplitudes and morphologies. For example, the non-inverting electrode on the forehead compared to the vertex can reduce the signal-to-noise ratio, resulting in a smaller waveform, but this is not a substantial effect. Placing the mastoid electrode farther from the ear (as is often done in threshold ABR testing) can reduce the amplitude of wave I.Impedances should generally be <5kΩ and inter-electrode impedances should ideally be <3kΩ for optimal recording [62].
In addition to the technical parameters of the ABR, variables dependent on the individual being tested also affect the results. As mentioned previously, the brain­stem of infants continues to mature until 18months of age. Therefore, longer laten­cies may be obtained [62].
There are also gender differences. Waves III, IV, and V are shorter in some adult females than in males. Differences in cochlear size have been suggested as a reason for this. It should be noted that these sex differences are small enough not to affect clinical normative values [63].
Another factor is the individual’s body temperature. A decrease in body tempera­ture can cause a prolongation of wave latencies and a reduction in amplitudes. Although not at levels that differ from normative values, it is helpful to record body temperature during testing for research purposes and intraoperative monitoring. It is recommended to use a correction factor of 0.2ms below 37°C and 0.15ms at each level for 38–42°C [64, 65].
Although pharmacological agents affect ABR results, especially in cases of hear­ing loss due to ototoxicity, drugs that do not directly affect hearing do not signi­cantly affect the latency and amplitude of ABR waves in clinical ndings. It has been noted that some anesthetics, which are sometimes utilized in order to perform the test under anesthesia in complex or difcult-to-test cases, cause prolongation of brainstem response latencies but have no signicant effect on amplitudes [66, 67].
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Neural Generators ofABRs
The ABR originates from various parts of the auditory nervous system, from the vestibulocochlear nerve (eighth nerve) to the upper brainstem. The generators of ABR components are thought to be as follows:
Wave I: Obtained from the distal part of the auditory nerve. Wave II: Obtained from the proximal part of the auditory nerve. Wave III: Originates from many nerve sources in the cochlear nucleus and superior
olivary complex regions. Wave IV-V: Wave IV-V is thought to be generated by neural activity as the lateral
lemniscus bers enter the contralateral inferior colliculus. However, it is reported
that there is more than one source for components responsible for wave III and
later peaks [6870].
Auditory Brainstem Response Analysis andInterpretation
The purpose of neurotological ABR evaluation is quite different from threshold determination. Neurotological ABRs can provide information about the location of a pathology in the auditory pathway. Detailed analyses of many wave components of the ABR waves, including their morphology, repeatability, absolute and interpeak latency values, amplitude relationships, and differences between the two ears, are particularly important for diagnostic ABRs [71].
Morphology refers to the general appearance of the resulting ABR wave. Because it requires the experience of the clinician, morphological analysis is sub­jective. The intensity level of the stimulus affects the morphology. As the intensity level decreases, the amplitude of the waveform decreases and the latency is longer. At a high-intensity stimulus level such as 80dB nHL, waves I, III, and V are seen. The most robust component is wave V; waves I and III can disappear at threshold levels [71].
The repeatability of a waveform is another aspect of morphology. Latency and amplitude values should be obtained under the same conditions [59, 71]. If the reli­ability of the waveform is low, this may indicate a retrocochlear pathology as a result of asynchronous/disrupted neural transmission [71].
Waves I, III, and V peak latencies obtained from each ear after stimulus presenta­tion are compared to normative data for latency assessment. The similarity of abso­lute latencies between the two ears is also examined. The latency of an ABR component reects the time it takes for neural activity to reach the neural generator/s [71]. ABR wave latencies increase steadily as stimulus intensity decreases. In nor­mal hearing, at the 80-dB nHL stimulus intensity level, wave I is obtained about
1.5ms after the stimulus and waves III and V occur at 2-ms intervals later than this. The obtained peak latencies, interpeak latencies, and interaural latency of wave V are compared with existing normative data [59, 71].
The latency–intensity function curve is a clinical graph that presents the decrease in latency as a function of increasing intensity (Fig.8.5). A clinician can easily compare the wave absolute latencies and I–III, III–V, and I–V interpeak latencies in the same ear or between the ears with normative data in this graph. The similarity of
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interpeak latencies between the two ears is evaluated. In general, the I–V interpeak latency should not exceed 4.5ms in adults and children over 18months of age. The I–V interpeak latency range in healthy newborns is 5ms. In symmetric or nearly symmetric hearing, the interaural difference of wave V peak latency should not exceed 0.3ms, otherwise a retrocochlear pathology should be suspected [71, 72]. An abnormality is dened as more than two standard deviations above the clinical mean (normative) or an appropriate normative database for the measurement of absolute wave latencies and interwave latency values.
For amplitude ratio assessment, wave V to wave I amplitude ratio is calculated. The result is compared with normative data. The amplitude of wave V is typically twice that of wave I, and the V/I amplitude ratio is 2.0. An amplitude ratio of <0.5 is considered abnormally reduced, suggesting a retrocochlear or auditory brainstem pathology. In infants younger than 18months with normal hearing, wave I ampli­tude is larger than wave V amplitude [71, 72].
In neurological evaluation, the accuracy or sensitivity of the ABR for auditory nerve lesions is high (>90%). The specicity is 85%–90% [72]. A functional prob­lem involving CN VIII and lower brainstem is evidenced by ABR abnormalities on the ipsilateral side, and rostral auditory brainstem pathology is mostly associated with contralateral ABR abnormalities [72, 73].
Clinical Use ofABRs forChildren
The purpose of newborn hearing screening is to detect the possibility of hearing loss, not to estimate the threshold. Therefore, the intensity level for screening has been set at 35dB nHL.If an ABR wave V is present at this level, the likelihood of signicant hearing loss is relatively low. The ABR has been endorsed by the Joint Committee on Infant Hearing (JCIH) as the standard for newborn hearing screen­ing [73].
In newborn hearing screening programs, ABR measurement can be performed with conventional instruments, but portable devices are now widely available. These devices include algorithms for automatic detection and analysis of wave V, provid­ing a “pass” or “refer” result. If there is no risk factor for newborns, the “pass” result means that the hearing system works well up to the upper auditory brainstem struc­tures. The “refer” result indicates that follow-up screening is needed (depending on the screening protocol), and the second “refer” result means a diagnostic hearing evaluation is required [73].
The OAE and automated ABR measurements were suggested by the JCIH to be used for newborn screening in 2007. However, OAE screening can miss cases of auditory neuropathy spectrum disorder. In addition, OAEs are extremely sensitive to minor middle ear disease, earwax, and measurement conditions. False positive results for OAE hearing screening and high referral rates due to technical issues can lead to increased costs and unnecessary anxiety for parents associated with the diag­nostic follow-up of infants. Therefore, ABRs alone or a combination of ABRs and OAEs is ideal for screening [73].
ABRs can also obtained with a bone vibrator used to determine bone conduction thresholds in pure-tone audiometry. This is a valuable test for determining bone