**3. Clinical ABR measurements**

### **3.1 Recording ABRs**

For clinical ABR measurements, an acoustical stimulus is presented to the patient and electrodes mounted to the skin of the head record the neural responses. Generally, short-duration stimuli are used, and the response is acquired in a timewindow of about 10–20 ms starting at stimulus onset. High-quality recordings require good contact between skin and recording system. Therefore, electrodes should be applied to the skin carefully to minimize the electric impedance between electrode and skin. Many different types of electrodes are available, both disposable and nondisposable. The quality of the electrodes and their application is of utmost importance for a high ABR recording quality. Essential is that inter-electrode impedance is kept below 5 kΩ, preferably below 3 kΩ. If this cannot be achieved, then at least the interelectrode impedances should be symmetric, for instance all-around 8 kΩ, as will be explained below. Inter-electrode impedance should be kept stable during the ABR assessment, so well-fixated electrodes are required.

For single-channel ABR-recording, one electrode (the so-called active electrode) is attached to the skin, generally at the midline of the head somewhere between forehead and nape. The ABR amplitude is higher when its position is closer to the vertex. A second electrode (also called the reference electrode) is attached at ear level, for instance, close to the upper border of the mastoid plane. The position of the third (ground) electrode is not very critical. Often, an off-midline location on the forehead is chosen (see **Figure 7**), but for a single-channel recording, the ear-level position at the contralateral ear can also be used. In that case, when changing stimulation side, the reference and ground electrode should be exchanged.

#### **Figure 7.**

*Measurement setup for a single channel ABR measurement with an electrode on the midline, an electrode at ear level, and a grounding electrode off mid-line on the forehead.*

ABR-potentials are also extremely small in comparison to other (interfering) potentials picked up by the electrodes. Therefore, high recording quality requires knowledge about the possible origins of these interferences and methods to reduce their strengths.

#### **3.2 Amplifying, filtering, and averaging of the ABR signal**

As ABR-potentials are in the range of 0.002–2 μV, amplification by a factor of 10,000–100,000 is required before the signals can be processed and interpreted. To achieve the high amplification factor that is required, differential amplifiers must be used. This type of amplifier has three connectors, two for input to the amplification channel (so-called plus and minus inputs) and one ground connector. Commonly, the midline (active) electrode is connected to the plus input, and the ear-level (reference) electrode is connected to the minus input. The third (ground) electrode is connected to the ground connector. In multi-channel ABR-recording systems, different channels share the active and the ground electrode. For each extra channel, only a separate reference electrode is needed. Often an ipsilateral ear-level electrode is used as a reference electrode for channel 1 and a contralateral ear-level electrode is used as a reference electrode for channel 2.

A differential amplifier suppresses the contribution of potential variations that are (approximately) common to the plus and minus input connectors, thereby reducing their contribution to the amplifier's output signal. The common-mode rejection ratio is the amplifier characteristic that reflects to what extent this suppression is successful. It should be at least 90 dB for high-quality ABR measurements. The common-mode rejection ratio degrades significantly when electrode impedances are too asymmetric, for instance, 2 kΩ for the reference electrode against 10 kΩ for the active electrode. So, inter-electrode impedance symmetry is essential for reaching a common-mode rejection ratio as high as is specified for the amplifier that is used.

Overloading the amplifier is unavoidable in ABR recording. Activation of head and neck muscles, for instance, may produce potential variations (EMG potentials) between the plus and minus connectors of 10–50 mV. To avoid overloading the first stage amplifier with an amplification factor of say 1000, the amplifier's output signal should be able to vary up to 10–50 V without saturating. Such a large output dynamic range of the amplifier requires a high power-supply voltage to avoid too many overloads. If the power supply of the amplifier cannot accommodate these high output levels, the output signal will saturate at its maximum or minimum extreme values and stay at that level for a time. Saturation generally occurs a little below the power-supply voltage. For instance, with a power supply voltage of 15 V, just below +15 V or −15 V.

One of the most important characteristics of the amplifier is its behavior when it recovers from overloads. This behavior is never listed in the specifications of the amplifier because the specifications only describe the normal functioning of the amplifier and not how it behaves after an overload. Some amplifiers show recovery behavior that makes them unfit for ABR recording, especially when the recovery potential waveform is a damped resonant. We advise to check this behavior of the amplifier, by using a single overloading pulse as the input signal.

Every ABR measurement system uses an analog bandpass filter in the input stage to suppress all non-ABR-related content of the input signal. Depending on the slopes of the passband, appropriate high pass and low pass cut-off frequencies should be selected. The steeper the slope in dB/oct, the lower the value of the high pass cut-off

frequency should be. For a slope of 24 dB/oct, the high pass cut-off frequency should be as low as 10–15 Hz. A quadrupling of that range is allowed for each halving of the slope. For example, for 6 dB/oct filter slope, the high pass cut-off frequency should be set at 160–240 Hz. The low pass cut-off frequency is less critical, as long as it is above 2 kHz for a slope of 6 dB/oct, with a quadrupling per doubling of the slope. After analog-to-digital conversion that occurs at some point in the signal processing, various filter designs can be used providing such filtering uses linear phase filters. In addition to amplification and filtering, four other methods are used to suppress the interfering potentials as much as possible to improve the quality of the ABRrecording: averaging, artifact-rejection, windowing, and alternating the stimulus polarity.

Most of the interfering potentials are not synchronous with stimulus onset but start randomly at a certain time point after stimulus onset. Consequently, at a specific time-point after stimulus onset, the measured electric potential amplitude consists of the ABR amplitude (signal) at that time-point and the sum of randomly distributed interfering potential amplitudes (noise). The first component (signal) is very weak compared to the second (noise). The signal, however, is causally related to the stimulus, while the noise varies randomly in amplitude and sign. By averaging the responses of many repeated fixed-level stimulus presentations, the values of the noise potential amplitudes tend to cancel each other, resulting in an average value of zero. The average of the ABR component, however, is not zero and its relative contribution increases with the increasing number of stimulus presentations. When calculating the average value after 1000–2000 stimulus presentations, the ABR component is generally stronger than the noise component and the ABR waveform emerges from the noise. For higher ABR amplitudes, commonly at higher stimulation levels, the number of averaged single-stimulus responses can be lower than at lower stimulation levels to arrive at the same ABR signal-to-noise ratio.

Averaging the response of multiple stimulus presentations increases the signalto-noise ratio drastically. The signal-to-noise ratio can be improved even more by a non-linear filter process called Artifact Rejection (AR). This process imposes a lower and upper limit on the electrode potential values that are accepted as valid measurements during a single registration at a fixed stimulus level. The idea is that if this value is exceeded during that registration, the response is dominated by interference and does not reflect the auditory nerve and brainstem responses. The upper and lower limit values are commonly set symmetrically as + and − a specific voltage value called the AR level. If any of the values in the sequence exceeds the AR level, the whole sequence is rejected for averaging. ABR systems in general allow the setting of the AR levels in μV, so for instance +/− 15 μV. For good quality ABR recording the AR level should be somewhere between 15 and 25 μV. Some ABR systems allow specification of the number of times that the AR levels may be exceeded before rejecting the whole sequence. For good-quality ABR recordings this number should be low, close to zero. Other signal averaging systems do not use stimulus amplitude as an AR criterion, but the AR rate. For instance, say that to have arrived at 1500 accepted responses for averaging, 1650 stimuli had to be presented. In other words, the responses to 1500 stimuli were accepted and the responses to 150 stimuli were rejected. In that case, the rejection count was 150, and the rejection rate was 150/1650. Setting an AR rate instead of absolute response amplitude levels for AR may result in accepting averages that are dominated by a few contaminated responses with high potential amplitudes, for example of myogenic origin. In terms of statistics, this approach may lead to a higher type II error

#### *Short-Latency Evoked Potentials of the Human Auditory System DOI: http://dx.doi.org/10.5772/intechopen.102039*

probability (i.e. the mistaken acceptance of a false null hypothesis). Therefore, we advise against the use of such averaging systems for clinical ABR assessment.

In unweighted averaging, every accepted response sequence after a stimulus presentation contributes equally to the average value after say 1500 stimulus presentations. In weighted averaging, however, each accepted response sequence is assigned a weight. This weight is calculated by some paradigm. For example, the weight could be determined by one over the variance of the sequence. This results in a final average with a larger contribution of the sequences with less interference (=lower variance). Manufacturers of ABR measurement systems generally do not specify the specific paradigm used in their system. Combining weighted averaging with AR is sometimes called Bayesian AR. This procedure uses weighted averaging for stimuli that are still within specified AR limits, assigning less weight to responses with higher amplitude. Responses with amplitudes that lie outside the AR limits are still rejected.

#### **3.3 Identifying interfering potentials**

To get a grip on the always present interference, one needs to know the origins of interfering potentials. The interfering noise can be synchronous to (or in sync with) the stimulus or not. In the first case, averaging does not help to reduce the amplitude of the interfering components. Furthermore, the interfering components can be of the physiologic origin or not.

Interfering potentials with a physiologic origin are potentials generated within the patient's body, e.g. by muscles, the brain, the eyes. Muscle activations are the most powerful source. Due to the differential type of amplification, only muscles at the head cause significant interference. Their interference comes in two different kinds. (1) In sync with the stimulus, caused by the (strong) auditory stimulation used with the ABR recording. The muscles involved are located postauricular (the muscles that can move the pinna) and in the neck (the sternocleidomastoid muscle). (2) Not-in-sync with the stimulus, caused by muscle activation at the level of head and neck, with muscles of the neck and jaw as major sources. The brain is also a source of interfering potentials, albeit normally much weaker than myogenic potentials in the ABR-frequency band. All brain activity not related to the auditory system causes interfering potentials. The eye is also a weak source of interference in the ABR-frequency band.

Non-physiological interference can be introduced by the recording and stimulation system itself, by other (medical) devices coupled to the patient, and by irradiation from external sources. The ABR-system can introduce interference by (1) the auditory stimulator used for eliciting the ABR, the so-called stimulus-artifact, or (2) error or poor electrical design of the system.

Generally, the stimulator contains an electrodynamic loudspeaker that generates an electromagnetic wave resulting from its coil movements. This waveform mirrors the electrical stimulus waveform (more specifically, convolved by the stimulator's impulse response). If this coil is close to electrodes or their leads an artefactual potential variation is introduced by electromagnetic induction. Obviously, this interfering potential is in sync with the stimulus and is not reduced in strength by averaging.

The most frequent causes of error are mains interference caused by ground loops originating in the amplifier and are caused by poor design of its power supply. For instance, the power supplies of the stimulus amplifier and the physiologic amplifier should be completely independent. If not, the supply voltage of the physiologic amplifier can suffer a dip when a strong stimulus is presented. Due to the extremely

high amplification factor of the physiologic amplifier, even a very small dip can cause a significant output signal variation. This may incorrectly be interpreted as input signal variation. Another example: in a multi-channel recording system the power supplies of the amplifiers of different channels should be independent and mutually completely decoupled to keep the common-mode-rejection factors independent.

Coupling of the patient to other medical equipment, like a heart-lung monitor in the intensive care unit or operation theater, often causes ground loops confounding the physiologic amplifiers' function with mains interference. The patient, the electrode wiring, and the pre-amplifier are also antennas that pick up the electromagnetic fields from the environment by induction. There is a multitude of possible sources, like radio broadcasting, wireless telephones, pagers, automatic doors, etc.

#### **3.4 Reducing interference**

Identification of the origins of the interfering signals requires inspection of the raw amplified electrode signal during the averaging process. This can be done by observing a free-running registration that is in sync with stimulus presentation.

When the difference in skin-electrode impedance is high for different electrodes (inter-electrode impedance), non-physiological interferences generate higher interfering potentials in the ABR measurement system. Therefore, keeping inter-electrode impedances below 5 kΩ and preferably below 3 kΩ, helps to reduce the interference induced by stimulus artifact and electromagnetic irradiation. If this interference is still too strong, it helps to lower the inter-electrode impedances even further down to under 1 kΩ.

The stimulus artifact has the waveform of the convolution of the electrical stimulus waveform and the stimulator's impulse response. With any waveform of the stimulus, there is first compression or reduction of the air pressure in the ear canal, the air is first condensed or first rarefied. The stimulus polarity is named accordingly: condensation or rarefaction. By alternating the electric stimulus polarity in the series of say 1500 stimuli used for one stimulation level, the alternating waveforms of the stimulus-artifact cancel each other from one stimulus to the next, because these are in anti-phase. At higher stimulation levels, however, the impulse response of the transducer might be somewhat asymmetric as to the phase, and therefore subsequent stimulus artifacts do not cancel exactly anymore. As a result, a stimulus artifact will remain present in the averaged response. This will occur specifically at levels close to the output limits of the transducer and with damaged transducers (after a drop to the floor for instance).

Increasing the number of averaged (accepted) responses increases the signal-tonoise ratio of the resulting ABR waveform. This only holds, however, for stationary noise. In clinical measurements, ABR interfering noise is in general very non-stationary in character. Therefore, averaging more than 2500 sweeps generally does not result in further improvement of the signal-to-noise ratio.

As myogenic potentials generate the strongest interference, the ABR-recording quality can be greatly improved by reducing muscle tension in the patient. This can be done by several conservative methods. (1) Placing the patient in a relaxing position in a special chair or on a bed, with special attention for a relaxed head position. (2) Keeping the patient's head position in the midline. Asymmetric pre-tension of both sternocleidomastoid muscles may lead to an asymmetric and stronger muscleartifact in sync with the stimulation. (3) Showing a (soundless and non-thrilling) video at a height that forces the patient to steer the eyes to the midline of the lower

#### *Short-Latency Evoked Potentials of the Human Auditory System DOI: http://dx.doi.org/10.5772/intechopen.102039*

half of the view field. When such measures do not suffice, additional (medical) measures can be taken, of course with medical authorization and/or control. (1) Giving relaxing drugs to the patient (obviously with authorized control). Some drugs, like ketamine, are unfit however because they provoke abnormal brain activity with higher interference in the ABR-frequency band as a result. (2) Giving full anesthesia with muscle relaxation and ventilation. In that case, however, care must be taken that the anesthesia is deep enough. Light anesthesia causes an enhancement in the higher-frequency components of the EEG, resulting in enhanced interference in the ABR-frequency band.

#### **3.5 Recording strategy**

To provide ABR-recordings with as much information as possible, the following procedures will help. (1) Make a two-channel recording at each stimulus level. (2) Create separate (sub)averages for different combinations of stimulus polarity, i.e. a (sub)average for condensation, rarefaction, and alternating polarity. (3) Create (sub) averages for test-retest measurements. (4) Record ABR responses at various levels of stimulation, spanning the (remaining) dynamic range of the auditory system for the side of stimulation, with five different levels if possible. (5) Present the different ABR recordings ordered vertically with the highest stimulus level on top. This creates an ABR pattern, that facilitates inspection of peak latency shift against stimulus intensity. If separate registrations for test-retest or condensation-rarefaction polarity are available, pairwise presentation per stimulus level is preferred. (6) Repeat steps 4–5 interactively during ABR assessment to arrive at the optimum result in the available time for assessment, "biding your time". This way the next stimulation level to be measured can be chosen optimally.

In two-channel recordings, the active electrode of an amplification channel is commonly positioned at the midline of the head, e.g. the vertex, and the reference electrodes at ear-level. With the reference-electrode at the side of stimulation, the ipsilateral ABR is recorded. With the reference electrode at the ear opposite to the side of stimulation, the contra-lateral ABR is recorded. The ipsi- and contralaterally measured ABR waveforms differ in specific aspects that can help to identify the ABR waveform peaks I–V. The most important differences are (1) peak III has a somewhat shorter latency in the contra-laterally derived ABR-waveform; (2) peak V has a somewhat longer latency in the contra-laterally derived ABR-waveform. With the ipsilateral recording projected right above the contralateral one in the visual representation, a kind of trapezoidal shape is visible in the peaks III–V combination. This greatly helps identifying that combination, specifically if the peak I–II combination is difficult or impossible to identify (see **Figure 8**).

The ABR waveforms for condensation and rarefaction stimulus polarities are not identical. This can only be made visible when responses for different stimulus polarities are recorded separately. A major problem with measuring the ABR responses for different stimulus polarities in different measurement runs is that due to the nonstationary nature of noise, these responses are measured under different interfering noise conditions. This can be avoided by measuring ABR responses with an alternating stimulus-polarity and storing the corresponding responses in separate data buffers. This allows creating subaverages for condensation and rarefaction stimuli that are acquired in similar noise conditions. When data of the different buffers are summed, the alternated average is still visible, but it can be split into two separate parts. Projecting the one superimposed on the other (with a different color for

#### **Figure 8.**

*Example of the simultaneous presentation of ipsi- and contralateral registration of ABR-response, showing the trapezoidal shape of the peak III–V complex.*

example) makes the differences between responses from condensation and rarefaction stimulus polarities visible. One obvious difference that stands out is the form of the stimulus-artifact, which is of opposite polarity. Concomitantly, if the cochlear microphonic response is detectable within the stimulus artifact, it will also show different polarity. Major differences can also occur in the morphology of III–V peak complex in cases of (steep) high-frequency cochlear hearing loss, as was explained in Section 2.4. These differences can be so large that identification of the III–V complex is ambiguous in responses obtained with alternating stimulus polarity, while identification is straightforward in the responses obtained with condensation or rarefaction polarity separately.

Additional information can also be derived by creating separate data buffers for alternating test and retest registration to again obtain subaverages acquired in similar noise conditions. Projecting test-retest subaverages on top of each other in different colors enables quick visual inspection of the stability of the acquired ABR responses, to determine if the ABR peaks robustly rise above the residual noise floor (see **Figure 9**). This can not only be judged subjectively, but the two subaverages also allow for quantitative calculations of various measures of similarity.

In summary, sorting the single stimulus responses into four data buffers, subaveraging and making various combined or split views of the results, yields easily available information on the stability of the results and of the differences between condensation and rarefaction responses.

Preferably five or more responses for different stimulation levels are acquired to construct an ABR pattern. As measurement time is often precious, due to the requirement of the patient remaining in a relaxed condition, it is best to aim at first acquiring *Short-Latency Evoked Potentials of the Human Auditory System DOI: http://dx.doi.org/10.5772/intechopen.102039*

#### **Figure 9.**

*An example of the presentation of test-retest subaverages. The upper registration shows a case with low test-retest reproducibility and the lower registration shows a case with high test-retest reproducibility.*

ABRs at higher stimulation levels and then at levels between 25 dB above and around the response threshold. In the lower-level range, the stimulus step size should be 10 or even 5 dB, while at levels far above threshold larger step sizes of 20 or even 25 dB can be used. Each succeeding stimulation level should be chosen as time-efficiently as possible. This can be achieved by constructing the ABR pattern each time acquisition at a specific stimulus level is completed. If a succeeding acquisition with a much lower stimulus level produces no ABR response, an educated guess should be made for the next higher level to be used.

The response threshold is defined as the lowest stimulation level at which reproducible response peaks (generally peak V) can be identified. At levels up to 20 dB above threshold and 5 dB below threshold, replication measurements are advised to confirm the presence or absence of response peaks. Note that for response threshold assessment, at least one acquisition must be obtained that shows no response peaks at all, preferably at a stimulation level just below (say 5 dB below) the lowest stimulation level that shows reproducible peaks in the response. Obviously, this is not necessary if response peaks are found at levels in the normal range of the response threshold, i.e. 0–20 dB(nHL). To enable good interpretation of the results for the various stimulation levels, it is very useful to order the recordings vertically according to decreasing stimulus levels, preferably in pairs of ipsi- and contralateral responses. This way of constructing the ABR pattern enables tracking of ABR peaks from high stimulus levels down to threshold, as is demonstrated in **Figure 8**.

#### **3.6 Interpreting ABRs**

The first step in ABR pattern interpretation is peak identification. The second step in the audiological use of the ABR pattern is determining its validity, i.e. whether the ABR pattern reflects the neural integrity of the auditory nerve and brainstem. The third step is determining the response threshold level. The fourth step is analyzing the relations between latency of the peaks and stimulus level.

First, identify peaks in the ABR pattern with equal or higher latency for decreasing stimulation level. At higher stimulation levels, say above 85 dB(nHL), peak

latencies may be stable, at lower stimulation levels peak latencies increase with decreasing stimulation level. Commonly this increase is larger when the stimulation level approaches the response threshold. Identification of the peak I–III–V complex is commonly easiest, and even more so with 2-channel recording with the ipsilateral averaged response positioned above the contralateral averaged response as shown in **Figure 8**. A trapezoidal shape should be observable in this complex, which positively identifies the III–V complex. Reproducibility of amplitude and latency of a peak at a constant stimulation level is required for reliable peak identification. As explained above, a test-retest view of the response pattern is very helpful. Easy switching between the views on the overall average and test-retest sub-averages helps to achieve greater reliability of peak identification.

Next, the peak I–II complex should be identified. Commonly the complex is better identifiable in the ipsilateral recording than in the contralateral recording. At high stimulation levels, over 85 dB(nHL), peak I prevails in amplitude and peak II is visible as a kind of shoulder on the downslope of peak I. At lower stimulation levels peak II tends to prevail in amplitude and peak I is visible as a kind of shoulder on the upslope of peak II. The transition range is between 55 and 65 dB(nHL) in normal hearing. Below 55 dB(nHL) peak I is rarely visible, but peak II can be. Mistakenly identifying peak II as peak I, yields an abnormally short time interval between this peak I and peak V. Identification of the I–II complex can be difficult or impossible in cases of significant conductive hearing loss. Then one must rely on the identification of the III–V complex for interpreting the ABR results.

Before performing audiometry based on the ABR pattern, the neural integrity of the auditory nerve, which is the source of the measured peak I and II potentials, should be assessed. This can be done by measuring the inter-peak interval, i.e. latency differences between peaks. For adults with normal auditory nerve function, the I–V latency difference should be below 4.3 ms. Larger differences are suspicious and the reliability of the audiometric interpretation of the pattern is questionable. These limits are agedependent, and for patients below 2.6 years, this limit value is higher. For term-born neonates it is 5.4 ms and for preterm neonates it is still higher. However, it must be kept in mind that absolute latencies can be prolonged due to a conductive hearing loss. In that case, the effective stimulation level of the cochlea is lower than the stimulation level by the amount of conductive loss. For each type of ABR system the normative values of the absolute latencies may differ somewhat, depending on the design and the stimulator used. Therefore, the absolute latencies of peak III and V at a specific stimulation level should preferably be compared to their normal range for that type of equipment setup.

With high-quality ABR-registrations, identification of the response threshold level is easy. In the case of moderate quality, identification is still possible but requires more expertise and experience. Two independent experienced judges will generally disagree by not more than 5–10 dB. For audiometric interpretation, the correspondence between the ABR threshold and pure tone threshold depends on the type of stimulus used, i.e. tonal or broadband. In the latter case, when a click stimulus is used, for example, the ABR threshold is strongly correlated with the pure-tone audiometric threshold at 3 kHz [31] as further discussed in Section 4. The latter being 10 dB less in dB(HL) than the ABR threshold in dB(nHL). In cases of very steep cochlear highfrequency hearing loss, the difference becomes larger, because the pure-tone frequency of highest correlation with the ABR threshold shifts downward. One should be on guard for this pitfall if shallower shapes of the ABR peaks are observed. For tonal stimuli, the relations between ABR threshold and pure-tone threshold depend strongly on the stimulus waveform used for eliciting the ABR.
