Athar Abdallatif Progress Report and Conversion Proposal

Progress Report and Conversion Proposal
The Progress Report for Master’s Research Candidature titled “Sensitivity and
specificity of the cervical vestibular evoked myogenic potential (cVEMP) evoked by
narrow band chirp stimuli in patients with vestibular disorders”
And
The Conversion Proposal to Ph.D. Research Candidature titled “Demystifying
the diagnostic usefulness of ocular and cervical vestibular evoked myogenic
potentials elicited by custom-built narrow band chirp stimuli among different types
of vestibular disorders”
Student’s Name: Athar Mazen Rasmi Abdallatif (P-SKM0010/20(R))
Main Supervisor: Dr. Wan Najibah Binti Wan Mohamad
Co-supervisor: 1) Assoc. Prof. Dr. Mohd Normani Bin Zakaria
2) Assoc. Prof. Dr. Rosdan Salim
Universiti Sains Malaysia
2021
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Table of Contents
1 Progress report...........................................................................................................1
1.1 Introduction...........................................................................................................1
1.1.1 Anatomy and physiology of the vestibular system........................................1
1.1.2 Vestibular assessment....................................................................................3
1.1.3 Vestibular evoked myogenic potential..........................................................3
1.1.4 Sensitivity and specificity of cVEMP............................................................4
1.1.5 Stimulus issues in cVEMP recording............................................................5
1.1.6 Problem statement.........................................................................................8
1.1.7 Study objectives...........................................................................................10
1.2 Methods...............................................................................................................10
1.3 Results.................................................................................................................12
1.3.1 Pilot study’s results......................................................................................12
1.3.1.1 Comparison in cVEMP results between (1000-100) Hz and (1000-
500) Hz downward narrow band chirp stimuli in healthy adults..........................13
1.3.2 Main study’s results.....................................................................................16
1.3.2.1 Demographic Data................................................................................16
1.3.2.2 Statistical analysis................................................................................19
1.3.2.2.1 Comparison in cVEMP results between 500 Hz tone burst and (1000-
100) Hz downward narrow band chirp stimuli in healthy and VD groups (within-
group comparisons)...............................................................................................20
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1.3.2.2.2 Comparison in cVEMP results between healthy and VD groups for 500
Hz tone burst and (1000-100) Hz downward narrow band chirp stimuli (between-
group comparisons)...............................................................................................23
1.4 Discussion...........................................................................................................35
1.4.1 Pilot study’s outcomes.................................................................................35
1.4.2 Main study...................................................................................................36
1.4.2.1 500 Hz tone burst and (1000-100) Hz downward narrow band chirp in
healthy group.........................................................................................................36
1.4.2.2 500 Hz tone burst and (1000-100) Hz downward narrow band chirp in
VD group 37
1.4.2.3 500 Hz tone burst between groups.......................................................37
1.4.2.4 (1000-100) Hz downward narrow band chirp between groups...........38
1.4.2.5 Effect of age on cVEMPs.....................................................................38
1.4.2.6 AUCs for tone burst and downward narrow band chirp stimuli.........39
1.4.2.7 Sensitivity and specificity for both stimuli...........................................39
1.5 Conclusion..........................................................................................................41
2 PhD conversion proposal.........................................................................................42
2.1 Background of study...........................................................................................42
2.1.1 vestibular disorders......................................................................................42
2.1.2 Vestibular evoked myogenic potentials (VEMPs)......................................43
2.1.3 Problem statement.......................................................................................45

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2.1.4 Objective of study........................................................................................46
2.1.4.1 General objective..................................................................................46
2.1.4.2 Specific objectives................................................................................47
2.1.5 Study hypothesis..........................................................................................47
2.2 Methodology.......................................................................................................48
2.2.1 Research design...........................................................................................48
2.2.2 Sample size requirement..............................................................................48
2.2.3 Inclusion and exclusion criteria...................................................................49
2.2.3.1 The inclusion criteria............................................................................49
2.2.3.2 The exclusion criteria...........................................................................49
2.2.4 Equipment....................................................................................................50
2.2.5 Procedure.....................................................................................................50
2.2.5.1 Stage 1..................................................................................................50
2.2.5.2 Stage 2..................................................................................................52
2.3 Ethical consideration...........................................................................................56
2.4 Statistical analysis...............................................................................................56
2.5 Research benefits................................................................................................56
2.6 Gantt chart...........................................................................................................58
3 List of publications...................................................................................................59
4 References.................................................................................................................60
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List of Tables
TABLE 1.1 COMPARISON OF CERVICAL VESTIBULAR EVOKED MYOGENIC POTENTIAL (CVEMP) BETWEEN
LEFT AND RIGHT EARS FOR (1000-100) HZ CHIRP STIMULUS..............................................................13
TABLE 1.2 COMPARISON OF CERVICAL VESTIBULAR EVOKED MYOGENIC POTENTIAL (CVEMP) BETWEEN
LEFT AND RIGHT EARS FOR (1000-500) HZ CHIRP STIMULUS..............................................................14
TABLE 1.3 INTERAMPLITUDE RATIO RESULTS FOR (1000-100) HZ AND (1000-500) HZ CHIRP STIMULI.......14
TABLE 1.4 THE RESULTS OF CERVICAL VESTIBULAR EVOKED MYOGENIC POTENTIAL (CVEMP) EVOKED BY
(1000-100) HZ AND (1000-500) HZ CHIRP STIMULI.............................................................................16
TABLE 1.5 COMPARISON OF CERVICAL VESTIBULAR EVOKED MYOGENIC POTENTIAL (CVEMP) TRIGGERED
BY 500 HZ TONE BURST AND (1000-100) HZ CHIRP IN HEALTHY GROUP. (DATA ARE EXPRESSED AS
MEAN (STANDARD DEVIATION) AND P VALUE USING PAIRED T-TEST)..................................................21
TABLE 1.6 COMPARISON OF CERVICAL VESTIBULAR EVOKED MYOGENIC POTENTIAL (CVEMP) TRIGGERED
BY TONE BURST AND CHIRP IN VESTIBULAR DISORDERED GROUP. (DATA ARE EXPRESSED AS MEAN
(STANDARD DEVIATION) AND P VALUE USING PAIRED T TEST.)............................................................22
TABLE 1.7 COMPARISON OF THE RESULTS OF THE CVEMP EVOKED BY 500 HZ TONE BURST BETWEEN
HEALTHY AND VESTIBULAR DISORDERED GROUPS BY USING INDEPENDENT T-TEST, ANCOVA (WITH
AGE AS THE COVARIATE) AND EFFECT SIZE...........................................................................................23
TABLE 1.8 COMPARISON OF THE RESULTS OF THE CVEMP EVOKED BY (1000-100) HZ CHIRP BETWEEN
HEALTHY AND VESTIBULAR DISORDERED GROUP BY USING INDEPENDENT T-TEST, ANCOVA (WITH
AGE AS THE COVARIATE) AND EFFECT SIZE...........................................................................................25
TABLE 1.9 THE RESULTS OF ROC STATISTICAL ANALYSIS FOR P1 LATENCY................................................27
TABLE 1.10 THE RESULTS OF ROC STATISTICAL ANALYSIS FOR N1 LATENCY.............................................29
TABLE 1.11 THE RESULTS OF ROC STATISTICAL ANALYSIS FOR P1 AMPLITUDE..........................................31
TABLE 1.12 THE RESULTS OF ROC STATISTICAL ANALYSIS FOR N1 AMPLITUDE..........................................32
TABLE 1.13 THE RESULTS OF ROC STATISTICAL ANALYSIS FOR INTERAMPLITUDE......................................34
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List of Figures
FIGURE 1.1 ANATOMY OF THE VESTIBULAR SYSTEM............................................................................................2
FIGURE 1.2 AN ILLUSTRATION OF RISE TIME, PLATEAU AND FALL TIME OF A TONE BURST............................5
FIGURE 1.3 WAVEFORMS OF CLICK AND TONE BURST STIMULI.......................................................................6
FIGURE 1.4 TYPES OF CHIRP STIMULI...............................................................................................................7
FIGURE 1.5 COMPARISON OF ABR WAVEFORMS PRODUCED BY CLICK AND CHIRP STIMULI...........................7
FIGURE 1.6 THE FLOW CHART OF RESEARCH METHOD...................................................................................11
FIGURE 1.7 THE CVEMP WAVEFORMS FOR BOTH STIMULI. THE UPPER CURVES ILLUSTRATE THE
WAVEFORMS FOR (1000-100) HZ DOWNWARD CHIRP STIMULUS, AND THE LOWER CURVES SHOW THE
WAVEFORMS FOR (1000-500) HZ DOWNWARD CHIRP STIMULUS. P1 AND N1 PEAKS ARE INDICATED. 12
FIGURE 1.8 GENDER DISTRIBUTION IN THE HEALTHY GROUP.........................................................................17
FIGURE 1.9 RACE DISTRIBUTION IN THE HEALTHY GROUP.............................................................................17
FIGURE 1.10 GENDER DISTRIBUTION IN VESTIBULAR DISORDERED GROUP....................................................18
FIGURE 1.11 THE RACIAL COMPOSITION OF THE VESTIBULAR DISORDERED GROUP......................................18
FIGURE 1.12 TYPES OF VESTIBULAR DISORDERS IN THE VESTIBULAR DISORDERED GROUP..........................19
FIGURE 1.13 RECEIVER OPERATING CHARACTERISTIC (ROC) CURVE FOR TONE BURST (STRAIGHT LINE) AND
CHIRP (DASHED LINE) STIMULI BASED ON P1 LATENCY OF CERVICAL VESTIBULAR EVOKED MYOGENIC
POTENTIAL (CVEMP)............................................................................................................................27
CHIRP (DASHED LINE) STIMULI BASED ON N1 LATENCY OF CERVICAL VESTIBULAR EVOKED MYOGENIC
POTENTIAL (CVEMP)............................................................................................................................29
CHIRP (DASHED LINE) STIMULI BASED ON P1 AMPLITUDE OF CERVICAL VESTIBULAR EVOKED
MYOGENIC POTENTIAL (CVEMP)..........................................................................................................30
CHIRP (DASHED LINE) STIMULI BASED ON N1 AMPLITUDE OF CERVICAL VESTIBULAR EVOKED
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CHIRP (DASHED LINE) STIMULI BASED ON INTERAMPLITUDE OF CERVICAL VESTIBULAR EVOKED
FIGURE 2.1 RECORDED RESPONSE OF C-VEMP (A) AND O-VEMP (B) IN ONE OF STUDY SUBJECTS. C-
VEMPS, CERVICAL VESTIBULAR-EVOKED MYOGENIC POTENTIALS; O-VEMP, OCULAR VEMPS........44
FIGURE 2.2 CERVICAL VESTIBULAR EVOKED MYOGENIC POTENTIAL (CVEMP) PARTICIPANT POSITION AND
ELECTRODES PLACEMENT......................................................................................................................53
FIGURE 2.3 OCULAR VESTIBULAR EVOKED MYOGENIC POTENTIAL (OVEMP) PARTICIPANT POSITION AND
ELECTRODES PLACEMENT.......................................................................................................................54
FIGURE 2.4 THE FLOWCHART OF THE STUDY METHOD...................................................................................55
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1 Progress report
This is the latest progress report for my masters research titled “Sensitivity
and specificity of the cervical vestibular evoked myogenic potential (cVEMP) evoked by
narrow band chirp stimuli in patients with vestibular disorders”. I am currently a full-time
MSc candidate and has started my study since 1 December 2020.
1.1 Introduction
The vestibular system provides a sense of balance in addition to
information about body position, allowing rapid compensatory movements in response to
both self-inflicted and external forces. Despite the fact that we are usually unaware of its
function, the vestibular system is an important component of both postural reflexes and
eye movements. If the system is compromised, it affects balance, control of eye
movements, and sense of orientation in space. Serious symptoms including vertigo,
nausea, floating sensation, imbalance and other types of dizziness would occur in those
with vestibular problems (Yoo & Mihaila, 2020).
1.1.1 Anatomy and physiology of the vestibular system

The inner ear is located within the petrous temporal bone and consists of
the cochlea, three semicircular canals that are sensitive to angular accelerations (head
rotations), and the otolith organs (utricle and saccule) that are sensitive to linear
acceleration, gravitational forces, and tilting of the head as illustrated in Figure 1 .1 (Yoo
& Mihaila, 2020).
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Figure 1.1 Anatomy of the vestibular system
The crista ampullaris is the sensory neuroepithelium of the semicircular
ducts, whereas the macula is the sensory neuroepithelium of the utricle and saccule. Both
neuroepithelial structures contain sensory cells known as hair cells. Each hair cell has
numerous stereocilia on its apical ends, which are arranged in rows according to their
length, and a single kinocilium on the lateral most end of the apical surface.
When the head is turned, the endolymph moves, causing the deflection of
stereocilia, leading to either depolarization or hyperpolarization. The vestibular nerve is
formed when the Scarpa ganglion’s afferent axons connect. Following that, the vestibular
nerve and the cochlear nerve fuse to form the vestibulocochlear nerve (8 cranial nerve).
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Which, in turn, transmits the neural impulses to the vestibular nucleus complex in the
brainstem, where they are processed. After that, the central system unifies all the nerve
signals coming from the ear, eye, head, and body to send them to either the thalamus,
cortex or cerebellum to control balance and orientation (Casale et al., 2020).
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1.1.2 Vestibular assessment
Previous research has revealed a wide range of reported vestibular
disorders, ranging from 6.1 percent to 35.4 percent (Nakashima et al., 2016). Vestibular
dysfunctions may impair postural control, balance, and visual stability in this population.
The vestibular disorders can be classified as peripheral, central, and mixed vestibular
disorders. The most common peripheral vestibular disorders that affect the balance
organs in the inner ear include benign paroxysmal positioning vertigo (BPPV), Meniere's
disease, vestibular neuritis, and superior canal dehiscence syndrome (SCDS). Central
problems, on the other hand, affect the parts of the central nervous system that
communicate with one another to maintain balance, such as brainstem vascular disease,
acoustic neuromas and tumors of the brainstem and cerebellum, multiple sclerosis, and
vertebrobasilar migraine (Balance & Dizziness Canada, 2021).
Assessment and diagnosis of vestibular disorders is through clinical
examinations (such as dix hallpike test, side lying test, head thrust test, etc.), objective
tests (electro/video-nystagmography [ENG or VNG], rotary chair, video head impulse
testing [vHIT], cervical/ ocular vestibular evoked myogenic potential [cVEMP/oVEMP],
etc.), and subjective tests (dizziness handicap inventory [DHI], vertigo symptom scale
[VSS], and so on). These tests are conducted to pinpoint the site of lesions so that proper
treatments can take place to minimize the negative consequences of vestibular disorders.
1.1.3 Vestibular evoked myogenic potential

In clinical settings, the functions of semicircular canals are conveniently
measured by established clinical assessments such as VNG, rotary chair, and vHIT tests.
On the other hand, limited clinical assessments are available to measure the function of
the otolith organs (saccule and utricle) that can also be compromised due to specific
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lesions affecting the vestibular system. The VEMP tests are the only assessments that can
measure the function of the otolith organs objectively. The cVEMP is one of the major
subtypes of VEMPs to measure the function of the ipsilateral saccule and inferior
vestibular nerve from the sternocleidomastoid muscle. The cVEMP waveform consists of
two prominent peaks: a positive peak (P1) with latency of around 13 ms, followed by a
negative peak (N1) with latency of around 23 ms. Another subtype is oVEMP which is
obtained from the inferior oblique eye muscle to reflect the function of the contralateral
utricle and superior vestibular nerve (Dlugaiczyk et al., 2020).
1.1.4 Sensitivity and specificity of cVEMP

Sensitivity and specificity values can be used as a guideline to identifiy the
accuracy of the cVEMP test. The proportion of persons who are true positive for the
disease in the entire population of people who have the disease is determined by
sensitivity, which is expressed as a percentage, whereas specificity represents the
probability of a negative test result in those who do not have the disease (Šimundić,
2009).
The percentage of abnormal cVEMP results in vestibular neuritis varied
from 36.6 to 80 percent. Whereas in Meniere's disease (MD) studies, there was a
significant link between the existence of cVEMP abnormalities and the presence of MD,
with amplitude reduction being the most common finding. In patients with BPPV,
cVEMP abnormalities ranged from 30-50 % (Godha et al., 2020: Scarpa et al., 2019).
The cVEMP responses were also found to be abnormal in superior canal dehiscence
(SSD), and the reported sensitivity and specificity were 86.5% and 87.8%, respectively
(Tran et al., 2020).
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1.1.5 Stimulus issues in cVEMP recording
Before the cVEMP test can be used in clinical settings, it is imperative to
have specific normative data based on the given population. Nevertheless, one of the
major factors that affects the normative data for cVEMP is the type of stimulus. This is
because the responses vary depending on the stimuli's characteristics (Choi, 2020).
Typically, 500 Hz tone burst is used to record cVEMP either in clinical
settings or for research purposes. This is because this stimulus has been proven to
produce the most consistent responses with large amplitudes, which is convenient when
testing both normal and vestibular disordered subjects (Ozgur et al., 2015). Tone bursts at
other frequencies (250 Hz, 1 kHz, 2 kHz, etc.) can also be used to record cVEMP but
their amplitudes were much smaller than those of 500 Hz tone burst (Cebulla & Walther,
2019). This is in line with the previous studies that support the superiority of the 500 Hz
tone burst in the cVEMP recording (Özgür et al., 2015: Zakaria et al., 2015). The typical
tone burst stimulus consists of specific rise time, plateau time and fall time, as illustrated
in Figure 1 .2.
Figure 1.2 An illustration of rise time, plateau and fall time of a tone burst

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The cVEMP test can also be conducted using click stimuli. However, the
cVEMP amplitudes were significantly smaller when stimulated by clicks, relative to the
500 Hz tone burst (Viciana & Lopez-Escamez, 2012). On the other hand, click stimuli
produce shorter cVEMP latencies compared to the 500 Hz tone burst (Cheng et al., 2003:
Wu et al., 2007). This is because clicks are characterized by a rapid onset, a short
duration, and a wide frequency range (Figure 1 .3) (Chertoff et al., 2010).
Figure 1.3 Waveforms of click and tone burst stimuli.
Recently, there is a growing interest to study the diagnostic usefulness of
cVEMP when tested with chirp stimuli (Aydın et al., 2021: Ocal et al., 2021: Moinudeen
et al., 2020). These chirp stimuli were initially developed and studied to improve the
waveforms in the auditory brainstem response (ABR) testing. In the ABR testing, the
mathematically designed chirp stimuli are able to overcome the cochlear traveling wave
delay and consequently, bigger responses are obtained (Wang et al., 2013: Aydın et al.,
2021). The examples of chirp stimuli are shown in Figure 1 .4. The ABR amplitudes
produced by the chirp stimuli are twice bigger than the amplitudes produced by the click
stimuli (Figure 1 .5).
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Figure 1.4 Types of chirp stimuli
Figure 1.5 Comparison of ABR waveforms produced by click and chirp stimuli
The first published study about cVEMP evoked by chirp stimuli was by
Wang and colleagues in 2013 involving 30 healthy adults. In particular, cVEMP results
were compared between click, 500 Hz tone pip and commercially available CE-chirp
stimuli. As reported, latencies were the shortest for CE-chirp stimulus (followed by click
and tone burst stimuli). On the other hand, interamplitude was comparable between tone
pip and CE-chirp stimuli (but was larger than that of click stimulus) (Wang et al., 2013).
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In a study by Özgür et al (2015) involving 39 healthy adults, cVEMP results were
compared between click, 500 Hz tone burst and chirp stimuli (500-4000 Hz). They then
found that the 500 Hz tone burst produced the longest latency, as well as the largest
amplitude. Recall that these studies employed the chirp stimuli with wider frequency
ranges for VEMP recording (Özgür et al., 2015: Wang et al., 2013).
Walther and Cebulla designed a band limited chirp stimulus (250-1000 Hz)
to record VEMP from healthy adults (n=10) and those with vestibular neuritis (n=6).
Among healthy subjects, it was found that VEMP amplitudes were the largest for the
chirp stimulus. Interestingly, VEMP latencies were the longest for the chirp stimulus
(Walther & Cebulla, 2016). A similar finding was observed in their subsequent study
(Cebulla & Walther, 2019). That is, the cVEMP latencies were longer for narrow band
chirp stimuli than for clicks.
1.1.6 Problem statement

Although the vestibular disorders occur in a relatively wide range of adults,
the available data on the sensitivity and specificity of cVEMP in discriminating vestibular
disorders in adults are inconsistent, ranging from 30%-90% and 40%-100%, respectively
(Egami et al., 2013: Lamounier et al., 2017: Kim-Lee et al., 2009). Studies are still
ongoing to further understand the role of cVEMP in diagnosing vestibular disorders and
obtain the respective normative data, as the results would differ according to the diseases
and several other factors including the recording parameters (Scarpa et al., 2019).
As mentioned earlier, the chirp stimuli have the potential in cVEMP
recording. Having cVEMP responses with larger amplitudes and shorter latencies would
be beneficial in clinical settings as the testing time can be reduced, and the response
variability is minimized (increased test reliability). However, some studies found larger
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cVEMP amplitudes and shorter VEMP latencies when tested with the chirp stimuli, while
contradictory outcomes were reported by others. The disagreements between the studies
might be contributed by different types of chirps used in the respective studies. In this
regard, there is a need to study the usefulness of cVEMP test when elicited by other types
of chirp stimuli. Furthermore, the literature on the performance of chirp-evoked cVEMP
test when testing patients with vestibular disorders is notably lacking.
It is worth mentioning that all published studies on chirp-evoked cVEMP
were carried out using the upward chirp stimuli, i.e., the frequencies are arranged from
low to high (e.g., 250-1000 Hz). In 2016, Syahirah and Mohd Normani developed a novel
custom-built downward chirp stimulus (1000-100 Hz, i.e., arranged from high to low
frequencies), and its usefulness was studied accordingly. Interestingly, the custom-built
downward narrow band chirp stimulus was found to produce the most optimum cVEMP
responses (i.e., the largest amplitudes and shorter latencies) compared to the upward
narrow band chirp stimulus (100-1000) Hz and the 500 Hz tone burst among healthy
subjects (Syahirah and Mohd Normani, 2016). Owing to this, it is of interest to further
explore the diagnostic value of cVEMP evoked by the downward narrow band chirp
stimulus when testing patients with vestibular disorders, which is the main focus of this
study. Additionally, it is also unknowm which type of the downward narrow band chirp
stimulus that is the most optimum to record cVEMP. In this respect, conducting a pilot
study would be beneficial to compare two different downward chirp stimuli with different
frequency content (1000-100 Hz versus 1000-500 Hz). The chirp stimulus that produces
the optimum cVEMP responses (i.e., larger amplitudes) will be chosen and used in the
subsequent phase of the study.
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1.1.7 Study objectives
This main aim of the study is to investigate the diagnostic usefulness of the
cVEMP evoked by the custom-built downward narrow band chirp stimulus in adult
patients with vestibular disorders (in comparisons to the conventional 500 Hz tone burst
stimulus). The specific study objectives are as follows:
1. To compare the cVEMP results between two different downward narrow band chirp
stimuli (1000-100 Hz and 1000-500 Hz) among healthy adults (within-group
comparisons).
2. To compare the cVEMP results between the custom-built narrow chirp and 500 Hz
tone burst stimuli among healthy adults (within-group comparisons).
3. To compare the cVEMP results between the custom-built narrow chirp and 500 Hz
tone burst stimuli among vestibular disordered adults (within-group comparisons).
4. To compare the cVEMP results between healthy and vestibular disordered adults for
each stimulus (between-group comparisons).
5. To determine the sensitivity and specificity of the cVEMP in detecting vestibular
disorders for each stimulus.
1.2 Methods
Figure 1 .6 shows the flow chart of the research method. The pilot study
was to determine the best frequency range for the downward narrow band chirp stimulus.
Then, the main study was divided into two stages: the first was the audiological
assessements, and the second was the application of cVEMP evoked by downward
narrow band chirp and 500Hz tone burst. In particular, the results of cVEMP tests were
compared between healthy and vestibular disordered adults using the appropriate
statistics.
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Figure 1.6 The flow chart of research method
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1.3 Results
1.3.1 Pilot study’s results
A pilot study was performed on 25 healthy adults aged between 22-45 years,
with a mean age 27.5 ± 7.6 years, who volunteered to be part of the study. This session
was conducted to identify the best frequency range for the downward chirp stimulus, any
potential problems or the need for appropriate modifications in order to have a smooth
data collection process.
All participants met the research criteria. cVEMPs were obtained in all
subjects in response to both (1000-100) Hz and (1000-500) Hz downward narrow band
chirp stimuli. The example of cVEMP waveforms of a representative subject for each
stimulus are shown in Figure 1 .7.
Figure 1.7 The cVEMP waveforms for both stimuli. The upper curves illustrate the
waveforms for (1000-100) Hz downward chirp stimulus, and the lower curves show the
waveforms for (1000-500) Hz downward chirp stimulus. P1 and N1 peaks are indicated.
1.3.1.1 Comparison in cVEMP results between (1000-100) Hz and
(1000-500) Hz downward narrow band chirp stimuli in healthy adults
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As shown in As shown in As shown in Table 1.1 and Table 1.2, there
were no significant differences in P1 latency, N1 latency, P1 amplitude, N1 amplitude
and interamplitude between right and left ears for the (1000-100) Hz chirp stimulus (P=
0.189, 0.658, 0.471, 0.129 and 0.183, respectively) and also for the (1000-500) Hz
stimulus (P=0.810, 0.456, 0.540, 0.611 and 0.894, respectively). and Table 1 .2, there
stimulus (P=0.810, 0.456, 0.540, 0.611 and 0.894, respectively). and Table 1 .2, there
stimulus (P=0.810, 0.456, 0.540, 0.611 and 0.894, respectively).
Table 1.1 Comparison of cervical vestibular evoked myogenic potential (cVEMP) between
left and right ears for (1000-100) Hz chirp stimulus.
(1000-100) Hz Left Right P value
P1 Amplitude 54.6 (19.8) 51.2 (20.99) 0.471
N1 Amplitude 58.7 (25.4) 51.6 (24.3) 0.129
Interamplitude 114.0 (40.8) 104.0 (36.999) 0.183
P1 Latency 16.96 (2.6) 17.5 (3.0) 0.189
N1 Latency 26.3 (3.0) 26.6 (3.2) 0.658
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Table 1.2 Comparison of cervical vestibular evoked myogenic potential (cVEMP) between
left and right ears for (1000-500) Hz chirp stimulus.
(1000-500) Hz Left right P value
P1 Amplitude 46.4 (19.8) 43.990 (18) 0.540
N1 Amplitude 47.3 (23.3) 48.8 (21.6) 0.611
Interamplitude 93.6 (38.9) 92.8 (33.1) 0.894
P1 Latency 18.5 (3.2) 18.4 (3.5) 0.810
N1 Latency 28.4 (2.9) 27.9 (3.3) 0.456
The interaural amplitude asymmetry ratio (IAR) was also calculated (left
ear amplitude - right ear amplitude/left ear amplitude + right ear amplitude). In
comparison between (1000-100) Hz and (1000-500) Hz chirp stimuli , P values for P1
amplitude, N1 amplitude, and interamplitude were 0.4593, 0.5998 and 0.5098,
respectively. The P values were all higher than 0.05 indicating that no significant
differences between left and right ears for both stimuli. as illustrated in The interaural
amplitude asymmetry ratio (IAR) was also calculated (left ear amplitude - right ear
amplitude/left ear amplitude + right ear amplitude). In comparison between (1000-100)
Hz and (1000-500) Hz chirp stimuli , P values for P1 amplitude, N1 amplitude, and
interamplitude were 0.4593, 0.5998 and 0.5098, respectively. The P values were all
higher than 0.05 indicating that no significant differences between left and right ears for
both stimuli. as illustrated in The interaural amplitude asymmetry ratio (IAR) was also
calculated (left ear amplitude - right ear amplitude/left ear amplitude + right ear
amplitude). In comparison between (1000-100) Hz and (1000-500) Hz chirp stimuli , P
values for P1 amplitude, N1 amplitude, and interamplitude were 0.4593, 0.5998 and
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0.5098, respectively. The P values were all higher than 0.05 indicating that no significant
differences between left and right ears for both stimuli. as illustrated in Table 1.3.
Collectively, since the left and right results were not statistically significant (P > 0.05),
the left and right data were then pooled for the subsequent analysis.. Collectively, since
the left and right results were not statistically significant (P > 0.05), the left and right data
were then pooled for the subsequent analysis.. Collectively, since the left and right results
were not statistically significant (P > 0.05), the left and right data were then pooled for
the subsequent analysis.
Table 1.3 Interaural amplitude asymmetry ratio(IAR) results for (1000-100) Hz and (1000-
500) Hz chirp stimuli
IAR (n=25) (1000-100) Hz (1000-500) Hz P value
P1 Amplitude 11.86 (4.08 - 19.81) 15.04 (6.96 - 23.31) 0.4593
N1 Amplitude 13.34 (5.74 - 26.12) 9.54 (4.52 - 19.995) 0.5998
Interamplitude 11.76 (3.68 - 19.66) 11.42 (1.31 - 19.07) 0.5098
As seen in Table 1 .4, in response to (1000-100) Hz chirp stimulus, mean
P1 latency, N1 latency, P1 amplitude, N1 amplitude and interamplitude were 17.3 ms,
26.4 ms, 52.9 μV, 55.1 μV, and 109.0 μV, respectively. In response to (1000-500) Hz
downward narrow band chirp, mean P1 latency, N1 latency, P1 amplitude, N1 amplitude
and interamplitude were 18.5 ms, 28.2 ms, 45.2 μV, 48.0 μV and 93.2 μV, respectively.
Descriptively, relative to the (1000-500) Hz chirp stimulus, the (1000-100 Hz) chirp
stimulus produced higher P1 and N1 amplitudes with shorter latencies (Table 1 .4). This
observation was then confirmed by the inferential paired t-test analysis. That is, as shown
15
in Table 1 .4, the P1 amplitude, N1 amplitude and interamplitude were found to be
significantly larger for the (1000-100) Hz chirp stimulus (P < 0.05). Relative to the
(1000-500) Hz chirp stimulus, the (1000-100) Hz produced significantly shorter P1
latency and N1 latency (P < 0.05). Based on the superior outcomes of the (1000-100) Hz
chirp stimulus, it was then selected to be used in the main study.
Table 1.4 The results of cervical vestibular evoked myogenic potential (cVEMP) evoked
by (1000-100) Hz and (1000-500) Hz chirp stimuli
N=50 (1000-100) Hz (1000-500) Hz P value
P1 Amplitude 52.9 (20.3) 45.2 (18.8) 0.001*
N1 Amplitude 55.1 (24.9) 48.0 (22.2) 0.005*
Interamplitude 109.0 (38.9) 93.2 (35.8) < 0.001*
P1 Latency 17.3 (2.8) 18.5 (3.3) 0.001*
N1 Latency 26.4 (3.1) 28.2 (3.1) < 0.001*
*Statistically significant at P < 0.05
1.3.2 Main study’s results

1.3.2.1 Demographic Data
In this study, 20 healthy subjects (40 ears) and 15 vestibular disordered
(VD) patients (30 ears) were enrolled. For the healthy group, the mean age was 32.6 ±
12.5 years; ranging from 22-60 years. Figure 1 .8 illustrates the gender distribution,
which showed that 30% of the participants were males and 70% were females. As shown
16
in Figure 1 .9, the healthy group consisted of 75% Malaysians, 5% Palestinians, 5%
Indians, and 15% were Chinese.
Gender Distribution in healthy group

Male
30%
Female
70%
Figure 1.8 Gender distribution in the healthy group
Race Distribution in healthy group

Chinese
15%
Indian
Palestinian5%
5%
Malaysian
75%
Figure 1.9 Race distribution in the healthy group
The mean age for the VD group was 41.8 ± 10.0 years, with a range of 21
to 59 years. The proportion of males was 34.5%, while 65.5% were females, as seen in
Figure 1 .10. All of them were Malaysians (Figure 1 .11).
The duration of having the vestibular disorders ranged from from six
months to 10 years. Figure 1 .12 displays the diseases distribution in this group.
17
Vestibular migraine and labyrinthitis were found in ten and two patients, respectively.
While vestibular neuritis, Meniere's disease and bilateral vestibulopathy were found in
one patient per each. However, none of the patients had conductive hearing loss or any
other conductive issues.
Gender Distribution in vestibular DISORDERD group
Male
35%
Female
66%
Figure 1.10 Gender distribution in the vestibular disordered group
The racial composition of the vestibular disordered group
Figure 1.11 The racial composition of the vestibular disordered group
18
TYPES OF VESTIBULAR DISORDERS IN VESTIBULAR
DISORDERED GROUP
Labyrinthitis
13%
7% Vestibular neuritis
7%
Meniere's disease
7%
67% Bilateral vestibulopathy
Vestibular migraine
Figure 1.12 Types of vestibular disorders in the vestibular disordered group
The chi-squared test for gender revealed no significant difference (P = 0.948)
for both groups, but the independent t-test for age exhibited a significant difference
between the healthy and VD groups (P = 0.002).
1.3.2.2 Statistical analysis

The cVEMP results, i.e., P1 latency, N1 latency, interamplitude, P1 latency
and N1 latency were computed for each subject. Both descriptive and descriptive
statistical analyses were used as applicable. Since the data were found to be normally
distributed (P > 0.05 by Kolmogorov-Smirnov test), parametric tests were carried out. In
particular, paired t-test was used to compare the cVEMP results between left and right
ears. The paired t-test was also used to compare the cVEMP results between the (1000-
100) Hz downward chirp stimulus and the conventional 500 Hz tone burst for each group.
To compare the cVEMP results for each stimulus between healthy and VD groups,
independent t-test was used. Since both groups had a statistically different mean age,
analysis of covariance (ANCOVA) was also used to compare the cVEMP results between
19
the two groups (with age as the covariate). Cohen’s effect size was measured to support
the P values. The effect size values were interpreted as small (d = 0.20), medium (d =
0.50) and large (d = 0.80) (Cohen, 1988). To determine the sensitivity and specificity of
cVEMP evoked by the two stimuli, receiver operating characteristic (ROC) was used.
The results were considered statistically significant at P < 0.05. All data analyses were
carried out using the MedCalc software.
1.3.2.2.1 Comparison in cVEMP results between 500 Hz tone burst and (1000-100)
Hz downward narrow band chirp stimuli in healthy and VD groups
(within-group comparisons)
Since no significant differences in all cVEMP results were found between
left and right ears, the left and right data were then pooled for the subsequent analyses. In
this matter, the results were analysed based on 40 ears for the healthy group and and 29
ears for the VD groups (a total of 69 ears).
Findings in the healthy group

In the healthy group, cVEMP responses were present in all subjects for both
the 500 Hz tone burst and (1000-100) Hz chirp stimulus (100% detectability). Table 1 .5
shows the cVEMP results for the two stimuli in the healthy group.
20
Table 1.5 Comparison of cervical vestibular evoked myogenic potential (cVEMP) triggered
by 500 Hz tone burst and (1000-100) Hz chirp in healthy group. (Data are expressed as mean
(standard deviation) and P value using paired t-test)
Healthy group 500 Hz Tone burst (1000-100) Hz Chirp P value

(mean (SD)) (mean (SD))
P1 Latency (ms) 14.9 (3.6) 13.1 (3.1) < 0.001*
N1 Latency (ms) 22 (4.3) 20.5 (3.7) < 0.001*
P1 amplitude (μV) 41.2 (23.1) 50.5 (27.2) 0.001*
N1 amplitude (μV) 61.4 (36.5) 83.2 (44.3) 0.001*
Interamplitude (μV) 96.6 (53.8) 128.1 (68.2) < 0.001*
SD: Standard Deviation
As seen in Table 1 .5, the mean P1 latency (13.1 ± 3.1 ms) and N1 latency
(20.5 ± 3.7 ms) for the (1000-100) Hz chirp were shorter than P1 latency (14.9 ± 3.6 ms)
and N1 latency (22 ± 4.3 ms) for the 500 Hz tone burst. The (1000-100) Hz chirp
stimulus also showed higher P1 amplitude (50.5 ± 27.2 μV), N1 amplitude (83.2 ± 44.3
μV), and interamplitude (128.1 ± 68.2 μV) than the 500 Hz tone burst (41.2 ± 23.1 μV,
61.4 ± 36.5 μV, and 96.6 ± 53.8 μV, respectively) .
The paired t-test was used to compare the cVEMP results evoked by the
(1000-100) Hz chirp with those evoked by 500 Hz tone burst stimuli. The P1 and N1
latencies were significantly shorter for the (1000-100) Hz chirp stimulus compared to the
500 Hz tone burst stimulus (P < 0.001). The chirp stimulus also showed significantly
higher P1 amplitude, N1 amplitude and interamplitude (P = 0.001, P < 0.001 and P <
0.001, respectively), relative to the 500 Hz tone burst.
Findings in the VD group

The cVEMP responses induced by the 500 Hz tone burst and (1000-100) Hz
chirp stimuli were successfully recorded from 29 ears (of 30 ears) suffering from
21
vestibular disorders (96.7% detectability). One ear did not respond to either chirp or tone
burst stimulus, so it was excluded from the analysis. Table 1 .6 shows the comparison of
tone burst evoked cVEMP results with chirp evoked cVEMP results.
Table 1.6 Comparison of cervical vestibular evoked myogenic potential (cVEMP) triggered
by tone burst and chirp in vestibular disordered group. (Data are expressed as mean (standard
deviation) and P value using paired t test.)
VD group 500 Hz Tone burst (1000-100) Hz Chirp P value

mean (SD) mean (SD)
P1 Latency (ms) 19.1 (4.1) 17.3 (4.2) < 0.001*
N1 Latency (ms) 24.8 (1.8) 22.9 (1.7) < 0.001*
P1 amplitude (μV) 23 (11.2) 25.4 (12.3) 0.062
N1 amplitude (μV) 32.6 (22.9) 32 (22.8) 0.694
Interamplitude (μV) 45.8 (36.2) 49.7 (36.7) 0.054
SD: Standard deviation VD group: vestibular disordered group
In response to the 500 Hz tone burst, mean P1 latency (19.1 ± 4.1ms), N1
latency (24.8 ±1.8ms) were desriptively longer than those for the chirp stimulus (17.3 ±
4.2 ms and 22.9 ± 1.7 ms, respectively). P1 amplitude, and interamplitude were higher for
the chirp stimulus (25.4 ± 12.3 μV and 49.7 ± 36.7 μV , respectively) compared to the
tone burst (23 ± 11.2μV, 32.6 and 45.8 ± 36.2μV, respectively). While the N1 amplitude
(32.6 ± 22.9μV) for the tone burst was slightly higher than the chirp stimulus (32 ± 22.8
μV).
As revealed by the paired t-test, there were no significant differences in P1
amplitude, N1 amplitude and interamplitude between the two stimuli (P = 0.062, 0.694,
and 0.054, respectively). On the other hand, the latencies of P1 and N1 of the (1000-100)
Hz chirp stimulus were significantly shorter than those of the 500 Hz tone burst (P <
0.001, P < 0.001, and P = 0.049, respectively).
22
1.3.2.2.2 Comparison in cVEMP results between healthy and VD groups for 500 Hz
tone burst and (1000-100) Hz downward narrow band chirp stimuli
(between-group comparisons)
Findings for the 500 Hz tone burst
As displayed in As displayed in As displayed in Table 1.7, when cVEMP
was evoked by the 500 Hz tone burst, the VD group showed longer P1 latency (16.7 ±
1.7ms) and N1 latency (24.6 ± 1.9ms) compared to the healthy group (14.6 ± 3.8 ms and
22 ± 4.3 ms, respectively). In addition, the P1 amplitude (22.1 ± 13.4 μV), N1 amplitude
(35.6 ± 26.6 μV), and interamplitude (53.8 ± 40 μV) were lower in the VD group than the
healthy group (39.4 ± 23.3 μV, 61.4 ± 36.5 μV and 95 ±53.8 μV, respectively)., when
cVEMP was evoked by the 500 Hz tone burst, the VD group showed longer P1 latency
(16.7 ± 1.7ms) and N1 latency (24.6 ± 1.9ms) compared to the healthy group (14.6 ± 3.8
ms and 22 ± 4.3 ms, respectively). In addition, the P1 amplitude (22.1 ± 13.4 μV), N1
amplitude (35.6 ± 26.6 μV), and interamplitude (53.8 ± 40 μV) were lower in the VD
group than the healthy group (39.4 ± 23.3 μV, 61.4 ± 36.5 μV and 95 ±53.8 μV,
respectively)., when cVEMP was evoked by the 500 Hz tone burst, the VD group showed
longer P1 latency (16.7 ± 1.7ms) and N1 latency (24.6 ± 1.9ms) compared to the healthy
group (14.6 ± 3.8 ms and 22 ± 4.3 ms, respectively). In addition, the P1 amplitude (22.1 ±
13.4 μV), N1 amplitude (35.6 ± 26.6 μV), and interamplitude (53.8 ± 40 μV) were lower
in the VD group than the healthy group (39.4 ± 23.3 μV, 61.4 ± 36.5 μV and 95 ±53.8
μV, respectively).
23
Table 1.7 Comparison of the results of the cVEMP evoked by 500 Hz tone burst between
healthy and vestibular disordered groups by using independent t-test, ANCOVA (with age
as the covariate) and effect size.
500 Hz tone burst Healthy group VD group P value ANCOVA Effect

(mean (SD)) (mean (SD)) size
P1 Latency (ms) 14.6 (3.8) 16.7 (1.7) 0.005 0.019 0.56
N1 Latency (ms) 22 (4.3) 24.6 (1.9) 0.005 0.033 0.77
P1 amplitude (μV) 39.4 (23.3) 22.1 (13.4) 0.003 0.005 0.91
N1 amplitude (μV) 61.4 (36.5) 35.6 (26.6) 0.004 0.036 0.81
Interamplitude (μV) 95 (53.8) 53.8 (40) 0.002 0.012 0.87
SD: Standard Deviation VD group: Vestibular disordered group
Based on the independent t-test, the VD group showed significantly lower P1
amplitude, N1 amplitude, and interamplitude compared with the healthy group (P =
0.003, P = 0.004, and P = 0.002, respectively). Moreover, significantly longer P1 latency
and N1 latency were observed in the VD group (P = 0.005 for both).
Findings for (1000-100) Hz downward narrow band chirp
Table 1 .8 illustrates the outcomes of cVEMP evoked by the (1000-100) Hz
chirp stimulus in healthy and VD groups. The results revealed that the healthy group had
shorter P1 latency (12.9 ± 3.2) and N1 latency (20.5 ± 3.7) than the VD group (14.9 ± 1.9
and 22.7 ± 1.9, respectively). The P1 amplitude, N1 amplitude, and interamplitude were
significantly higher in the healthy group (46 ± 27.2, 80.3 ± 43.9 and 122.6 ± 66.8,
respectively) compared to VD group (26.4 ± 15.2, 36 ± 26.7 and 62.4 ± 40.5,
respectively).
24
Table 1.8 Comparison of the results of the cVEMP evoked by (1000-100) Hz chirp between
healthy and vestibular disordered group by using independent t-test, ANCOVA (with age as
the covariate) and effect size.
(1000-100) Hz Healthy group VD group P value ANCOVA Effect size

chirp (mean (SD)) (mean (SD))
P1 Latency (ms) 12.9 (3.2) 14.9 (1.9) 0.007* 0.029* 0.75
N1 Latency (ms) 20.5 (3.7) 22.7 (1.9) 0.008* 0.039* 0.74
P1 amplitude (μV) 46 (27.2) 26.4 (15.2) 0.001* 0.005* 0.89
N1 amplitude (μV) 80.3 (43.9) 36 (26.7) < 0.001* < 0.001* 1.22
Interamplitude (μV) 122.6 (66.8) 62.4 (40.5) < 0.001* 0.001* 1.09
SD: Standard Deviation VD group: Vestibular disordered group

The independent t-test showed that there were significant differences in all
cVEMP parameters (P1 latency, N1 latency, P1 amplitude, N1 amplitude, and
interamplitude, with P < 0.05) between the two groups.
The 500 Hz tone burst and (1000-100) Hz chirp results were also analysed
using the ANCOVA test, with age as the covariate. The ANCOVA results for P1 latency,
N1 latency, P1 amplitude, N1 amplitude, and interamplitude (P = 0.029, P = 0.039, P =
0.005, P < 0.001, P = 0.001) supported the results of the independent t-test,
demonstrating that the cVEMP results were statistically different between the two groups,
after controlling for the age effect.
Effect size analyses were also performed for all cVEMP parameters. For
both stimuli, medium effect sizes were found for P1 and N1 latency, whereas P1
amplitude, N1 amplitude, and interamplitude exhibited big effect sizes. The effect size
values for P1 latency, N1 amplitude, and interamplitude were greater for the (1000-100)
Hz chirp stimulus than for the 500 Hz tone burst (Tables 1.7 and 1.8). This suggests that
25
the differences in cVEMP parameters between the healthy and VD groups were larger
and substantial when tested with (1000-100) Hz chirp stimulus, relative to the VD group.
1.3.2.2.3 Receiver-operating characteristic (ROC)
Receiver-operating characteristic (ROC) analysis was used to determine the
ability of the 500 Hz tone burst and (1000-100) Hz chirp stimuli in distinguishing the VD
group from the healthy group based on the cVEMP parameters. In particular, information
on area under curve (AUC), sensitivity and specificity, and comparisons between ROC
curves was gathered. In order to measure the sensitivity and specificity of the respective
VEMP parameter, the ideal cut-off value was calculated using Youden Index.
ROC for P1 latency

Figure 1 .13 shows the ROC curve for both stimuli. Descriptively, they
looked comparable, and a further analysis was required to unveil the diagnostic property
of these stimuli. Table 1 .9 indicates the ROC analysis with the respective statistical
values. As revealed, both of AUCs were significantly higher than 0.5 (P = 0.010 and
0.004 for tone burst and chirp, respectively). As such, both 500 Hz tone burst and (1000-
100) Hz chirp stimuli were found to have a good diagnostic value in distinguishing
between the healthy group and the VD group based on the P1 latency of cVEMP. With a
cut-off value of 15.4 ms, the sensitivity and specificity of cVEMP were 82.8% and
60.0%, respectively for the 500 Hz tone burst. For the chirp stimuli, the sensitivity and
specificity were 92.3% and 44.1%, respectively when 12.7 ms was used as the cut-off
value. When the AUCs were compared between the two stimuli, no significant difference
was found between them (P = 0.797).
26
Figure 1.13 Receiver operating characteristic (ROC) curve for tone burst (straight line)
and chirp (dashed line) stimuli based on P1 latency of cervical vestibular evoked
myogenic potential (cVEMP).
Table 1.9 The results of ROC statistical analysis for P1 latency.
AUC P value Cut-off point Sensitivity Specificity

(ms) (%) (%)
500 Hz tone burst 0.680 0.010* >15.4 82.8 60
(1000-100) Hz chirp 0.693 0.004* >12.7 92.3 44.1
ROC for N1 latency
27
Figure 1 .14 displays that the ROC curve for the (1000-100) Hz chirp
stimulus and the 500 Hz tone burst. As shown in Table 1 .10, both of AUCs were
significantly large (P = 0.006 and 0.010 for tone burst and chirp, respectively). Thus,
based on the N1 latency of cVEMP, both 500 Hz tone burst and (1000-100) Hz chirp
stimuli were found to have good diagnostic value in discriminating between the healthy
and VD groups. The sensitivity and specificity of cVEMP for the 500 Hz tone burst were
92.9% and 51.3%, respectively, with a cut-off value of 21.8 ms. When 19.5 ms was
selected as the cut-off value for the chirp stimuli, the sensitivity and specificity were
100% and 41%, respectively. When the AUCs were compared between the two stimuli,
there was no significant difference between them (P = 0.775).
28
and chirp (dashed line) stimuli based on N1 latency of cervical vestibular evoked
Table 1.10 The results of ROC statistical analysis for N1 latency.

(ms) (%) (%)
500 Hz tone burst 0.680 0.006* >21.8 92.9 51.3
(1000-100) Hz chirp 0.672 0.010* >19.5 100 41.0
ROC for P1 amplitude
29
The ROC curves based on P1 amplitude for the two stimuli are shown in
Figure 1 .15. The results of ROC statistical analysis for P1 amplitude in Table 1 .11
showed that the 500 Hz tone burst and the (1000-100) Hz chirp have significantly higher
AUCs than 0.5 (P < 0.001 for both stimuli). With a cut-off value of 21.4 ms, cVEMP had
56.5% sensitivity and 80% specificity for the 500 Hz tone burst. Whereas, the sensitivity
and specificity of the chirp stimuli were 55.6% and 91.4%, respectively, when 19.1 ms
was used as the cut-off value. When the AUCs of the two stimuli were compared, there
was no significant difference (P = 0.755).
and chirp (dashed line) stimuli based on P1 amplitude of cervical vestibular evoked
30
Table 1.11 The results of ROC statistical analysis for P1 amplitude.

(ms) (%) (%)
500 Hz tone burst 0.737 <0.001* ≤21.4 56.5 80
(1000-100) Hz chirp 0.734 <0.001* ≤19.1 55.6 91.4

ROC for N1 amplitude
The ROC curves for the 500 Hz tone burst and (1000-100) Hz chirp stimuli
appear comparable based on N1 amplitude (Figure 1 .16). Table 1 .12 expresses the
ROC statistical analysis. As noted, both of AUCs were significant (P < 0.001 for both).
cVEMP has 56% sensitivity and 94.6% specificity for the 500 Hz tone burst with a cut-
off value of 25.2 ms. While when 27.2 ms was chosen as the cut-off value, the chirp
stimuli had 55.6% sensitivity and 100% specificity. However, When the AUCs of the
tone burst and chirp stimuli were compared, a significant difference was observed (P =
0.005). Thus, (1000-100) Hz chirp stimulus was found to have a higher diagnostic value
in distinguishing between healthy group and VD group based on the N1 amplitude of
cVEMP.
31
and chirp (dashed line) stimuli based on N1 amplitude of cervical vestibular evoked
Table 1.12 The results of ROC statistical analysis for N1 amplitude

(ms) (%) (%)
500 Hz tone burst 0.745 <0.001* ≤25.2 56.0 94.6
(1000-100) Hz chirp 0.822 <0.001* ≤27.2 55.6 100

ROC for interamplitude
32
Figure 1 .17 illustrates the ROC curves of the (1000-100) Hz chirp and 500
Hz tone burst stimuli for interamplitude of cVEMP. As shown in Table 1 .13, both of
AUCs were significant (P < 0.001 for both). cVEMP has 57.7% sensitivity and 86.1%
specificity for the 500 Hz tone burst with a cut-off value of 41 ms. the chirp stimuli had
55.6% sensitivity and 100% specificity ,when 45 ms was chosen as the cut-off value.
Nevertheless, there is a significant difference between the AUCs of the two stimuli when
they were compared (P = 0.015). Therefore, based on interamplitude parameter of
cVEMP, the chirp stimuli was better in distinguishing between the healthy and VD
groups.
and chirp (dashed line) stimuli based on interamplitude of cervical vestibular evoked
33
Table 1.13 The results of ROC statistical analysis for interamplitude.

(ms) (%) (%)
500 Hz tone burst 0.759 <0.001* ≤41 57.7 86.1
(1000-100) Hz chirp 0.787 <0.001* ≤45 55.6 100

34
1.4 Discussion
It is worth mentioning that the literature on cVEMP evoked by chirp
stimuli is limited (approximately ten published articles as of year 2021). Overall, the
results of this study clearly show that the custom-built downward narrow band chirp
(1000-100) Hz stimulus is more effective and sensitive to record cVEMP, relative to the
conventional 500 Hz tone burst stimulus. The respective discussions are described in the
subsequent paragraphs. .
1.4.1 Pilot study’s outcomes

Recall that a pilot study was conducted to determine which type of
downward chirp stimulus that would produce the most optimum cVEMP responses. It
was then found that cVEMP waveforms with higher amplitudes and shorter latencies
were elicited by the (1000-100) Hz chirp stimulus, compared to the (1000-500) Hz chirp
stimulus. This was the first study carried out to unveil the cVEMP responses evoked by
different types of downward chirp stimuli, making the comparisons with other studies
difficult. In this regard, the superiority of the (1000-100) Hz chirp stimulus might be due
to its larger frequency range (and therefore, more energy to record cVEMP).
Additionally, by analyzing the interaural difference in cVEMP (between the two ears)
elicited by the two stimuli, no obvious interaural differences were found, which is rather
expected. This finding is in line with those of Ocal et al. (2021), that found that no
difference in asymmetry between the ears for both 500 Hz tone burst and 500 Hz narrow
band CE-chirp (360-720 Hz) stimuli. When Kumar et al. (2021) employed the 500 Hz
tone burst stimulus to evoke the cVEMP, they found no statistically significant difference
in IAR for both 500 Hz tone burst stimulus and 500 Hz narrow band CE-chirp (360-720
Hz) stimulus, which is likewise consistent with our findings.
35
1.4.2 Main study
1.4.2.1 500 Hz tone burst and (1000-100) Hz downward narrow band
chirp in healthy group
In the present study, our custom-built chirp stimulus elicits greater
amplitudes than the tone burst stimulation of the same intensity (90 dBnHL). As a result,
identifying the response in cervical VEMP is much easier, thus the higher the amplitude,
the less the examiner's errors will be (Aydın et al., 2021). This is in line with the findings
of Wang et al. (2014), Walther & Cebulla (2016), Moinudeen et al. (2020) and Aydın et
al (2021). One of the aspects that can explain the difference in amplitude is the stimulus's
frequency content. Tone bursts are short, single-frequency stimuli with slower rise and
fall times, whereas our chirp stimulus have broader frequencies with faster rise and fall
times.
The latencies of c-VEMP for chirp in the healthy group were found to be
earlier than those for tone bursts, which is consistent with Wang et al. (2014), Moinudeen
et al. (2020), Ocal et al. (2021) and Aydın et al. (2021). Early latencies are due to
stimulus design, as concluded by Zakaria et al. (2015), and are not related to any
physiological considerations.
1.4.2.2 500 Hz tone burst and (1000-100) Hz downward narrow band

chirp in VD group
The downward narrow band chirp stimulus was used for the first time in
the VD patients in our study. There are no studies in the literature that compare the
36
downward narrow band chirp to other stimuli to determine which stimulus is more
benificial when testing VD patients. Because diverse stimuli and different vestibular
disorders were employed to collect and analyze the cVEMP, it is difficult to compare the
results of this study, in which the majority of VD group were vestibular migraine
patients, to other studies.
However, in our study when the chirp cVEMP and tone burst cVEMP
findings were compared in the VD group, differences were observed only for P1 and N1
latencies, both values were significantly shorter for the chirp stimulus. No significant
differences were found for P1 amplitude, N1 amplitude and interamplitude.
1.4.2.3 500 Hz tone burst between groups

According to our findings, P1 amplitude, N1 amplitude, interamplitude, P1
latency, and N1 latency can distinguish VD patients from normal people when cVEMP
was induced by the 500Hz tone burst, since the VD group showed significantly lower P1
amplitude, N1 amplitude, and interamplitude compared with the healthy group.
Moreover, significantly longer P1 latency and N1 latency were also observed in the VD
group.
Many studies using the 500Hz tone burst and click stimuli at 95, 100, and
105 dB nHL reported significant differences in latency and amplitude measurements in
vestibular patients compared to the control group (Zaleski et al., 2015: Korres et al.,
2011: Gunes et al., 2020: Akkuzu & Gu, 2006: Salviz et al., 2016). However, no
significant differences in cVEMP measurements across groups were seen in other
studies using the 500 Hz tone burst stimulus at 90 and 100 dB nHL (Hong et al., 2011:
Ueno & Goto, 2021).
37
Differences in the stimulations utilized to elicit cVEMPs (stimulus type,
frequency, and intensity), the types of vestibular patients included in the study, or the
patients' ages could be the causes of the discrepancy between these studies.
1.4.2.4 (1000-100) Hz downward narrow band chirp between groups

Similar to the 500 Hz tone burst, the downward narrow band chirp
demonstrated a good diagnostic value in distinguishing between vestibular and healthy
groups based on P1 latency, N1 latency, P1 amplitude, N1 amplitude, and interamplitude.
According to our study's effect size analysis, the chirp stimulus had larger
effect sizes for all cVEMP parameters except N1 latency and P1 amplitude, which were
slightly higher for tone burst stimulus. Therefore, the down chirp stimulus was
considered more effective than the 500 Hz tone burst in distinguishing between vestibular
patients and healthy individuals.
1.4.2.5 Effect of age on cVEMPs

Age has been shown to have a consistent effect on VEMP responses, with a
decrease in amplitude and an increase in latency as people get older. The loss of neurons
inside the medial vestibular nucleus that occurs with aging may be linked to the reduction
in the vestibulocollic reflex (Viciana & Lopez-Escamez, 2012). Because of the mean age
difference between the two groups in our study, we considered the age as the covariate in
the ANCOVA analysis. The results revealed that after controlling for the age effect, there
were still significant differences between groups in the outcomes of both 500 Hz tone
burst and (1000-100) Hz chirp stimuli.
1.4.2.6 AUCs for tone burst and downward narrow band chirp stimuli
The 500 Hz tone burst stimulus showed significantly large AUCs for all
cVEMP parameters. The AUCs ranged from 0.680 - 0.759. The largest AUC (0.759) was
38
observed for Interamplitude, whereas the smallest one (0.680) was found for P1 and N1
latencies.
The downward narrow band chirp stimulus also showed significantly large
AUCs for all parameters, ranged from 0.672-0.822. N1 amplitude produced the largest
AUC (0.822), while the smallest AUC was noted for N1 latency.
When the AUCs of the two stimuli were compared, they showed no
significant differences based on P1 latency, N1 latency, and P1 amplitude. In contrast, for
N1 amplitude and interamplitude, the chirp stimulus produced significantly larger AUCs
compared to the 500 Hz tone burst.
Taken together, both the 500 Hz tone burst and the (1000-100) Hz chirp
stimuli were found to be useful in discriminating between the healthy and VD groups, but
the chirp stimulus was more effective.
1.4.2.7 Sensitivity and specificity for both stimuli

In our study, cVEMP's sensitivity for the 500 Hz tone burst ranged from
56.0%-92.9%. The highest sensitivity (92.9%) was observed for N1 latency, while the
lowest sensitivity (56.0%) was noted for N1 amplitude. The specificity for the 500 Hz
tone burst ranged from 51.3%-94.6%. The highest specificity (94.6%) was found for N1
amplitude, whereas the N1 latency produced the lowest specificity (51.3%).
The sensitivity and specificity of 500 Hz and 1000 Hz tone bursts were
greater in the literature than our findings. The explanation for this is the type of vestibular
dysfunction that was studied. The sensitivity range for Meniere's disease studies is
62.7%-93%, and the specificity range is 78%-95% (Jariengprasert et al., 2017:
Lamounier et al., 2017: Salviz et al., 2016: Kim-Lee et al., 2009). Furthermore, SCD
experiments revealed that sensitivity and specificity were 100% and 93%, respectively
39
(Hunter et al., 2017: Park et al., 2015). The sensitivity and specificity of cVEMP induced
by 500 Hz tone burst were 100% and 95%, respectively, in Kumar's study, which
included patients with retrosigmoid vestibular schwannoma excision and
labyrinthectomy. (Kumar et al., 2021)
Nevertheless, our sensitivity and specificity results were much higher than
the previous studies that investigated the diagnostic accuracy of cVEMP in patients with
vestibular migraine. Sensitivity range was 19.6%-29.3%, whereas the specificity range
was 48.9%-96.9% (Jariengprasert et al., 2017: Egami et al., 2013). In relation to our
study, since most of the VD patients were diagnosed to have vestibular migraine (66%),
lower sensitivity values of cVEMP parameters were expected. Furthermore, all cVEMP
parameters elicited by the 500 Hz tone burst revealed significant AUC values, indicating
that the cVEMP testing has adequate diagnostic property.
cVEMP's sensitivity for the chirp stimulus in our study ranged from 55.6%-
100%. N1 latency produced the maximum sensitivity (100%), while P1 amplitude, N1
amplitude, and Interamplitude had the lowest sensitivity (55.6%). The specificity for the
chirp stimulus ranged from 41.0%-100%. The highest specificity (100%) was found for
N1 amplitude and interamplitude, whereas the lowest specificity was obtained for N1
latency (41.0%).
For both downward narrow band chirp and tone burst stimuli, N1 latency
was found to be the most sensitive parameter (100% and 92.9%, respectively). N1
amplitude and interamplitude are the most specific parameters for chirp stimulus (100%
specificity), while the most specific parameter for tone burst stimulus is N1 amplitude
(94.6%).
40
1.5 Conclusion
In the pilot study, the results demonstrate that the (1000-100) Hz chirp is
better than (1000-500) Hz chirp in evoking the cVEMP responses. In the main study, the
comparison between the (1000-500) Hz chirp stimulus and the 500 Hz tone burst
stimulus revealed that both stimuli were found to be useful in discriminating between the
healthy and VD groups. However, the novel (1000-100) Hz chirp stimulus is more
efficient and sensitive to record cVEMP. As such, the findings of this study support the
idea of having an alternative stimulus for easier peak recognition and analysis in the
cVEMP recording (in conjunction with the tone burst stimuli, which are now utilised in
clinics around the world). To make generalisations, more research is needed with bigger
sample sizes and specific vestibular disease groups.
41
2 PhD conversion proposal
2.1 Background of study
2.1.1 vestibular disorders
The term "vestibular disorder" refers to a collection of over 25
conditions. Vestibular disorders that affect the balance organs in the inner ear (vestibular
system) are classified as peripheral problems, such as benign paroxysmal positioning
vertigo (BPPV); the labyrinth becomes sensitive to gravitational forces as the utricular
neuroepithelium degenerates, resulting in the detachment of otoconia, which freely foat
in semicircular canals (SCCs) or attach to the cupula. Meniere's disease; is charecterized
by endolymphatic hydrops or excess endolymph in the endolymphatic space. it is a
multifaceted chronic illness that manifests as recurrent vertigo attacks, fluctuating
hearing loss, tinnitus, and auditory fullness. Vestibular neuritis is a viral infection of the
vestibular nerve (inferior, superior, or both branches) or ganglion. And superior canal
dehiscence syndrome (SCDS); a "third opening" or "third window" forms between the
superior semicircular canal and the middle cranial fossa as a result of a bone defect in the
canal in this disease (Balance & Dizziness Canada, 2021: Diaz et al., 2017: Kutlubaev et
al., 2021) .
Central vestibular problems, on the other hand, impact the parts of the central
nervous system (brain), affecting the integration and processing of sensory input from the
vestibular, visual, and somatosensory systems. The most common central disorders
include brainstem vascular disease, acoustic neuromas and tumors of the brainstem and
cerebellum, multiple sclerosis, and vertebrobasilar migraine; both migraine and
vertiginous symptoms are common and frequently coexist. Vestibular problems can also
be classified as mixed problems. Vestibular disorders occur when any part of this delicate
42
and complex process is harmed by disease, injury, or aging (Balance & Dizziness
Canada, 2021).
Patients with vestibular disorder undergo routine vestibular assessment
including: first, the clinical examination such as the dix hallpike test, which assesses the
semicircular canals as it is is widely regarded as the gold standard for the identification of
the posterior canal benign paroxysmal positional vertigo (BPPV), and head thrust test,
that is one of the bedside methods used to provide information about how well the
vestibular ocular reflex compensates for a change in head position. Second, objective
tests as electro/video-nystagmography (ENG or VNG) to evaluate the inner ear and
central motor functions, video head impulse testing (vHIT) to determine disorders of the
vestibulo-ocular reflex and identify which ear is affected in cases of peripheral vestibular
loss, and cervical/ ocular vestibular evoked myogenic potential (cVEMP/oVEMP ), etc.)
to assess the otolith organs (utricle and saccule) and the vestibular nerve. Finally, the
subjective tests as dizziness handicap inventory (DHI) (Madzharova & Beshkova, 2020:
Andera et al., 2020).
The focus of this study is on the cVEMP and oVEMP tests as they are recent
tests and studies on its application in vestibular diseases are increasing.
2.1.2 Vestibular evoked myogenic potentials (VEMPs)

As previously mentioned, vestibular evoked myogenic potentials (VEMPs)
are otolith-driven vestibular reflexes stimulated by loud sound which is conducted by air
conduction (AC), bone-conducted vibration (BCV), or galvanic vestibular stimulation.
VEMPs are classified as ocular VEMPs (oVEMPs) or cervical VEMPs (cVEMPs)
depending on where the recording electrodes are placed and where the response
originates.
43
Cervical VEMPs (cVEMPs) are obtained from the ipsilateral
sternocleidomastoid muscle to reflect the function of the saccule and inferior vestibular
nerve. The c-VEMP response consists of peak-and-trough is also known as an initial
positivity (P1 or P13) followed by a negativity (N1 or N23), which is based on the
milliseconds at which those responses typically occur (Dlugaiczyk et al., 2020: Hain &
Cherchi, 2021).
Ocular VEMPs (oVEMPs) are obtained from the contralateral inferior
oblique eye muscle to reflect the function of the utricle and superior vestibular nerve. The
oVEMPs waveform is composed of an initial negative peak (N10 or N1) and a
subsequent positive peak (P15 or P1) post stimulus onset as illustrated in Figure 2 .
18(Kousht et al., 2020).
Figure 2.18 recorded response of cVEMP (a) and oVEMP (B) in one of study subjects.
cVEMPs, cervical vestibular evoked myogenic potentials; oVEMP, ocular vestibular
evoked myogenic potentials.
44
Tone bursts, clicks, and chirps are the three forms of stimuli that can be used
to record VEMPs. The 500 Hz tone burst is the standard stimulus used clinically because
it produces the most consistent responses with large amplitudes, making the results easier
to interpret and for clinical diagnosis. The literature suggests that the tone burst
stimulation has greater latencies than the click stimulation. This is assumed to be related
to tone burst's longer rise/fall period (Özgür et al., 2015).
Even if the 500 Hz tone burst stimulus has been accepted as the standard
stimulus in the VEMP tests, an alternative stimulus to produce more robust VEMP
waveforms is required to improve the current clinical protocols. As shown in my
Master’s research, the custom-built downward narrow band chirp stimulus (1000-100) Hz
produced more robust cVEMP responses, relative to the conventional 500 Hz tone burst.
It is also more sensitive in detecting vestibular disorders. Thus, this chirp stimulus will be
used in my proposed PhD research to record both cVEMP and oVEMP responses in
different groups of vestibular disorders.
2.1.3 Problem statement

The 500 Hz tone burst is commonly used to record VEMPs in clinical
settings. In contrast, the chirp stimulus is the most commonly used stimulus in the
auditory tests (e.g., auditory brainstem response) due to its ability to produce the
maximum response by providing the cochlear with the optimal stimulation that results in
simultaneous nerve firing. Thus, it increases the ABR amplitude (Ocal et al., 2021).
In line with these recent studies, many of them have demonstrated the
advantage of the chirp over the tone burst due to its high amplitudes and short latencies.
However, many variables and factors may influence the outcomes of the VEMP tests, the
best stimulus for recording VEMP is still arguable, and previous studies have not clearly
45
mentioned the standard values that are acceptable to all (Özgür et al., 2015: Truong,
2015). Thus, in my Master’s research, the normative values of cVEMP were determined
using the novel custom-built narrow band chirp stimulus. The sensitivity and specificity
of this test were also calculated to determine its accuracy. In addition to that, there is no
knowledge about the waveform characteristics of cVEMP in response to narrow band
chirp stimulus in vestibular disordered cases, so changes in cervical VEMPs were
monitored and the outcomes were evaluated.
The ocular VEMP (with the new downward chirp) was added in the
proposed PhD study because the ocular and cervical VEMPs provide complementary
information about the saccular and utricular otolithic function, as the testing of ocular and
cervical VEMPs allows the crossed vestibulo-ocular reflex and ipsilateral sacculo-collic
reflex to be determined. Therefore, conducting these tests together may increase the
sensitivity and specificity of detecting vestibular disorders. Moreover, the outcomes of
the master's study were assessed after all types of vestibular disorders were pooled into a
single group. Whereas the efficiency of both cVEMP and oVEMP in each subtype of
vestibular disorders, such as Menier's disease, vestibular migraine, benign paroxysmal
positional vertigo (BPPV), and labyrinthitis/vestibular neuritis, will be explored
separately in the PhD project.
2.1.4 Objective of study

2.1.4.1 General objective
To examine the usefulness of the oVEMP and cVEMP evoked by the novel
downward narrow band chirp stimulus in detecting various types of vestibular disorders.
2.1.4.2 Specific objectives
46
1. To compare oVEMP and cVEMP results between the (1000-100) Hz narrow band
chirp stimulus and the 500 Hz tone burst in healthy individuals (within-group
comparisons).
2. To compare oVEMP and cVEMP results between the (1000-100) Hz narrow band
chirp stimulus and the 500 Hz tone burst in different types of vestibular disorders (within-
group comparisons).
3. To compare oVEMP and cVEMP results between healthy and vestibular disordered
groups for each stimulus (between-group comparisons).
4. To determine the sensitivity and specificity of the oVEMP and cVEMP in detecting
vestibular disorders for each stimulus.
5. To determine the overall sensitivity and specificity of the combined oVEMP and
cVEMP findings in detecting vestibular disorders.
2.1.5 Study hypothesis

Null hypothesis, Ho
-There is no significant difference in the cVEMP and oVEMP results when using (1000-
100) Hz narrow band chirp stimulus compared to 500 Hz tone burst in healthy group and
in the VD groups.
-There is no significant difference in the oVEMP and cVEMP results between the healthy
group with the VD groups when using (1000-100) Hz narrow band chirp stimulus or 500
Hz tone burst.
- The AUCs of the oVEMP and cVEMP are not significantly higher than 0.5 for each
stimulus.
47
- The AUCs of the combined oVEMP and cVEMP are not significantly higher than 0.5
for each stimulus.
Alternative hypothesis, Ha
-There is a significant difference in the cVEMP and oVEMP results when using (1000-
100) Hz narrow band chirp stimulus compared to 500 Hz tone burst in healthy group and
in the VD groups.
-There is a significant difference in the oVEMP and cVEMP results between the healthy
group with the VD groups when using (1000-100) Hz narrow band chirp stimulus or 500
Hz tone burst.
- The AUCs of the oVEMP and cVEMP are significantly higher than 0.5 for each
stimulus.
- The AUCs of the combined oVEMP and cVEMP are significantly higher than 0.5 for
each stimulus.
2.2 Methodology
2.2.1 Research design
This study is case-control observational study design. Figure 2 .21 shows the
flow chart of the proposed method.
2.2.2 Sample size requirement

The sample size was calculated using MedCalc software version 20.006
(MedCalc Software Ltd, Ostend, Belgium; https://www.medcalc.org; 2021) and based on
the study by (Salviz et al., 2016). By choosing area under curve ROC option, alpha value
= 0.05, power of study = 0.90, area under curve = 0.731, null hypothesis value = 0.50, the
48
number of samples required is 30 for each group. By considering 10% dropout, this study
will recruit 33 subjects for each group. Since 5 groups of subjects will be studied, the
total of number of subject required is 165.
2.2.3 Inclusion and exclusion criteria

2.2.3.1 The inclusion criteria
- For healthy group
1. People between the ages of 18-59 years.
2. No neurological, vestibular or otological illnesses.
3. Normal middle ear function according to PTA and tympanometry results.
- For vestibular disordered group s
1. People between the ages of 18-59 years.
2. No otological illnesses.
3. Normal middle ear function according to PTA and tympanometry results.
4. Diagnosed with Benign paroxisimal positional vertigo (BPPV), Labyrinthitis/
vestibular neuritis, Menier’s disease, or vestibular migraine.
2.2.3.2 The exclusion criteria

- Anyone will be excluded from the healthy group if:
1. S/He has a history of vestibular disorders or comorbidities affecting the vestibular
system.
2. S/He is taking effective mindfulness medications.
3. S/He has incomplete results.
- Anyone will be excluded from the vestibular disordered group if:
1. S/He is taking effective mindfulness medications.
49
2. S/He has incomplete results.
2.2.4 Equipment
1) otoscope
2) Tympanometer
3) Audiometer
4) cVEMP
5) oVEMP
2.2.5 Procedure
2.2.5.1 Stage 1
In order to avoid any conductive problem, participants are initially
subjected to basic audiological testing after taking a detailed medical case history. Firstly,
all participants will undergo to otoscopic examination, this is done by making sure the
otoscope light is turned on and using a sterile speculum. To straighten the external
auditory canal, the pinna will be pulled upwards and backward. The otoscope will be
positioned in the external auditory meatus, as the otoscope should be held like a pencil in
the right hand for testing the participant’s right ear and vice versa for the left ear, and rest
the examiner's hand against the participant’s cheek for stability. This will prevent injury
to the ear if there is sudden movement. Drainage, ear canal debris, ear canal collapse,
position of the tympanic membrane, general appearance of the tympanic membrane, color
of the tympanic membrane, vascularity of the tympanic membrane, signs of liquid present
in the middle ear, and perforations of the tympanic membrane were all recorded as
otoscopic judgments of the external auditory meatus and tympanic membrane.
Following that, a Tympanometer (GSI TympStar Pro) will be used to
measure the movement of the ear drum and middle ear function. A probe-like device will
50
be inserted into the participant's ear canal, after which the instrument will alter the
pressure in the ear, generate a pure tone, and measure the eardrum responses to the sound
at various pressures. This results in a tympanogram, which shows how admission changes
with pressure. The tympanic membrane and middle ear are normal on a type A
tympanogram (no conductive problem).
Pure Tone Audiometry (PTA) (Audiometer GSI 61) will then be used to
assess hearing thresholds. Pure tone audiometric air conduction testing will be performed
by presenting a pure tone to the ear through an earphone and measuring the threshold
which is the lowest intensity in decibels (dB) at which this tone is perceived 50% of the
time at all frequencies, 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz, and 8000 Hz for
each ear. Bone conduction testing is done by placing a bone vibrator on the mastoid
process and measuring the threshold at (250-4000) Hz. In order to prevent the nontest ear
from participating in the test, masking noise is occasionally used.
The difference between the results of air conduction thresholds and bone
conduction thresholds is known as the air bone gap. A 15 dB or more an air bone gap
means the presence of conductive pathology. Before the data collection, all of these
devices will be calibrated properly.
Participants in the main study (oVEMP and cVEMP tests) will be those
who pass all of the basic audiological tests (otoscopic examination: normal appearance of
external auditory canal and tympanic membrane, Tympanometry: Type A, and Pure tone
audiometry: no air- bone gap).
2.2.5.2 Stage 2
Chirp stimulus
51
The (100-1000) Hz downward narrow band chirp will be used, which
contains frequencies in the sensitivity range (around 500 Hz) that elicit VEMPs in
response to air conduction.
VEMPs recording
Five groups of eligible participants (healthy group and four vestibular
disordered groups) will undergo oVEMP and cVEMP recording in a sound proof room.
Each participant will be given adequate explanation and instructed to relax in order to
reduce interference. For cVEMP testing an active electrode will be placed on the upper
third of the sternocleidomastoid muscle (SCM), a reference electrode will be placed on
the medial clavicle, and a ground electrode will be placed on the low forehead. The
surface of skin will be scrubbed using conductive gel to reduce impedance. Participant
will be instructed to turn her/his head to the contralateral side until the lateral margin of
the SCM can be seen during the recording period (Figure 2 .19).
Figure 2.19 Cervical vestibular evoked myogenic potential (cVEMP) participant position
and electrodes placement
52
For oVEMP, after skin preparation, the participant will be asked to maintain
focus on a specific visual target on the opposite wall, which is 2 meters away and at a 30-
degree upward angle with the horizontal plane. As illustrated in Figure 2 .20, the active
electrode will be positioned 1 cm beneath the free edge of the inferior eyelid on the
opposite side of the stimulation (near to the inferior oblique muscle on the skin). The
reference electrode will be placed contralateral to the stimulation in the internal canthus,
and the ground electrode will be put on the forehead (Mat et al., 2021).
Figure 2.20 Ocular vestibular evoked myogenic potential (oVEMP) participant position
and electrodes placement
Unilateral (100-1000) Hz down narrow band chirp and 500 Hz tone burst will
be use as the stimulation delivered at an intensity of 95 dB nHL through calibrated insert
phones in a random order to reduce the effect of muscular fatigue.
53
To ensure adequate levels of activation and to enable fine adjustment of the
head position, we will monitor the participants to match the EMG levels for each side and
to allow measurement of the background contraction levels and the calculation of the
normalized amplitudes.
For each ear and each stimulus, we'll calculate the interamplitude, P1
amplitude, N1 amplitude, as well as P1 and N1 latencies. After that, we will compare: 1-
the results of the oVEMP and cVEMP between the (1000-100) Hz narrow band chirp
stimulus and the 500 Hz tone burst in each group of the vestibular disorders, and in the
healthy group in terms of amplitude and latency. 2 - the results of the oVEMP and
cVEMP between healthy group and vestibular disordered groups for each stimulus. In
addition to that, the information on area under curve (AUC), sensitivity and specificity,
and comparisons between ROC curves will be gathered.
54
Figure 2.21 The flowchart of the study method
2.3 Ethical consideration
This research will be carried out only after the Jawatankuasa Etika
Penyelidikan Manusia (JEPeM) USM has given its ethical approval after extension.
55
2.4 Statistical analysis
The cVEMP and oVEMP results will be obtained. Both descriptive and
inferential statistical analyses will be used as appropriate. The mean, standard deviation,
percentage, etc. will be used to describe the results.
The data would be tested for normality and balance of variance before being
used in inferential analyses. The paird t-test will be used to compare between the 500 Hz
tone burst and (1000-100) Hz downward chirp stimuli in the same group. Whereas the
independent t-test (or Mann Whitney test) and ANCOVA test will be used to compare
test results between the healthy group and the different types of vestibular disorders
groups. The receiver operating characteristic (ROC) curve method will be applied to
determine the sensitivity and specificity of the cVEMP and oVEMP evoked by (1000-
100) Hz downward narrow band chirp and 500 Hz tone burst in detecting each type of the
vestibular disorders.
2.5 Research benefits

At the end of the session, the participant will be able to know the state of
his/her hearing status and parts of the balance system bilaterally. This may take a little
while after the session, as the researcher needs to summary all the test results.
The overall results of the study will be presented at national and/or
international conferences. These results also will be published in scientific journals.
The results of the study may benefit this community, as oVEMP and
cVEMP test will be used using a new stimulus with high sensitivity and specificity,
which will help us to reach a better diagnosis of disorders of the balance system.
56
2.6 Gantt chart
2021 2022
PROJECT ACTIVITIES
DEC JAN FEB MAR APR MAY JUN JUL AUG SEPT OCT NOV DEC
Gather the participants and get their X X X X

approval
Applying the auditory tests on the X X X X X X
participants.
Recording oVEMPs and cVEMP X X X X X X
Comparing the results between the X X X X X

two groups and the two stimuli
Data Analysis X X X X X X X X X
Final report and publication X X X X X X X
57
3 List of publications
1. ABDALLATIF ATHAR M R, 2021, Is it beneficial to have chirp stimuli in vestibular
evoked myogenic potential (VEMP) testing? , International Journal on Disability and
Human Development.
2. ABDALLATIF ATHAR M R, 2021, Earlier peak latencies may not fully reflect the
robustness of cervical vestibular evokedmyogenic potential to CE-chirp stimulus,
Journal of Audiology and Otology.
* Two more papers are currently being written and will be released soon.
58
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Athar Abdallatif Progress Report and Conversion Proposal

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Progress Report and Conversion Proposal

specificity of the cervical vestibular evoked myogenic potential (cVEMP) evoked by

narrow band chirp stimuli in patients with vestibular disorders”

The Conversion Proposal to Ph.D. Research Candidature titled “Demystifying

the diagnostic usefulness of ocular and cervical vestibular evoked myogenic

Student’s Name: Athar Mazen Rasmi Abdallatif (P-SKM0010/20(R))

Main Supervisor: Dr. Wan Najibah Binti Wan Mohamad

Co-supervisor: 1) Assoc. Prof. Dr. Mohd Normani Bin Zakaria

2) Assoc. Prof. Dr. Rosdan Salim

Universiti Sains Malaysia

1.1.1 Anatomy and physiology of the vestibular system........................................1

1.1.2 Vestibular assessment....................................................................................3

1.1.3 Vestibular evoked myogenic potential..........................................................3

1.1.4 Sensitivity and specificity of cVEMP............................................................4

1.1.5 Stimulus issues in cVEMP recording............................................................5

1.1.6 Problem statement.........................................................................................8

1.1.7 Study objectives...........................................................................................10

1.3.1 Pilot study’s results......................................................................................12

1.3.1.1 Comparison in cVEMP results between (1000-100) Hz and (1000-

500) Hz downward narrow band chirp stimuli in healthy adults..........................13

1.3.2 Main study’s results.....................................................................................16

1.3.2.1 Demographic Data................................................................................16

1.3.2.2 Statistical analysis................................................................................19

1.4.1 Pilot study’s outcomes.................................................................................35

1.4.2 Main study...................................................................................................36

1.4.2.3 500 Hz tone burst between groups.......................................................37

1.4.2.4 (1000-100) Hz downward narrow band chirp between groups...........38

1.4.2.5 Effect of age on cVEMPs.....................................................................38

1.4.2.7 Sensitivity and specificity for both stimuli...........................................39

2 PhD conversion proposal.........................................................................................42

2.1 Background of study...........................................................................................42

2.1.1 vestibular disorders......................................................................................42

2.1.2 Vestibular evoked myogenic potentials (VEMPs)......................................43

2.1.3 Problem statement.......................................................................................45

2.1.4.1 General objective..................................................................................46

2.1.4.2 Specific objectives................................................................................47

2.1.5 Study hypothesis..........................................................................................47

2.2.1 Research design...........................................................................................48

2.2.2 Sample size requirement..............................................................................48

2.2.3 Inclusion and exclusion criteria...................................................................49

2.2.3.1 The inclusion criteria............................................................................49

2.2.3.2 The exclusion criteria...........................................................................49

2.2.5.1 Stage 1..................................................................................................50

2.2.5.2 Stage 2..................................................................................................52

2.3 Ethical consideration...........................................................................................56

2.4 Statistical analysis...............................................................................................56

2.5 Research benefits................................................................................................56

2.6 Gantt chart...........................................................................................................58

LEFT AND RIGHT EARS FOR (1000-100) HZ CHIRP STIMULUS..............................................................13

LEFT AND RIGHT EARS FOR (1000-500) HZ CHIRP STIMULUS..............................................................14

(1000-100) HZ AND (1000-500) HZ CHIRP STIMULI.............................................................................16

MEAN (STANDARD DEVIATION) AND P VALUE USING PAIRED T-TEST)..................................................21

(STANDARD DEVIATION) AND P VALUE USING PAIRED T TEST.)............................................................22

AGE AS THE COVARIATE) AND EFFECT SIZE...........................................................................................23

AGE AS THE COVARIATE) AND EFFECT SIZE...........................................................................................25

TABLE 1.9 THE RESULTS OF ROC STATISTICAL ANALYSIS FOR P1 LATENCY................................................27

TABLE 1.10 THE RESULTS OF ROC STATISTICAL ANALYSIS FOR N1 LATENCY.............................................29

TABLE 1.11 THE RESULTS OF ROC STATISTICAL ANALYSIS FOR P1 AMPLITUDE..........................................31

TABLE 1.12 THE RESULTS OF ROC STATISTICAL ANALYSIS FOR N1 AMPLITUDE..........................................32

TABLE 1.13 THE RESULTS OF ROC STATISTICAL ANALYSIS FOR INTERAMPLITUDE......................................34

FIGURE 1.1 ANATOMY OF THE VESTIBULAR SYSTEM............................................................................................2

FIGURE 1.3 WAVEFORMS OF CLICK AND TONE BURST STIMULI.......................................................................6

FIGURE 1.4 TYPES OF CHIRP STIMULI...............................................................................................................7

FIGURE 1.6 THE FLOW CHART OF RESEARCH METHOD...................................................................................11