User manual | An investigation of the Auditory P300 Event Related Potential across gender. FD Lombard

University of Pretoria etd – Lombard, F D (2005)
An investigation of the Auditory
P300 Event Related Potential across
gender.
FD Lombard
Department of Communication Pathology
Faculty of Humanities
University of Pretoria
February 2005
University of Pretoria etd – Lombard, F D (2005)
Acknowledgements
As always with projects like these, there are many people standing on the
sidelines, cheering you on and throwing there full weight behind you, to get
you to the finishing line. To all these people I express my deepest gratitude. A
special thank you to the following people;
Mamma:
‘Richer than gold, you may have tangible wealth untold
Caskets of jewels and coffers of gold
Richer than I you can never be; I had a mother who read to me.’
-
Stricland Gillilan –
Pappa & Annelize: ‘Nothing is a strong as gentleness and nothing is so
gentle as Real strength’.
Helena & Cobus:
Anon-
‘Cherish your vision and your dreams as they are the
children of your soul; the blueprints of your ultimate
achievements’
-
Cobus Marais:
Napoleon Hill-
‘Liebe ist alles, die sie bis zu ist… es wert ist wirklich für
zu kämpfen, geknackt wird und ist für to, fer und riskiert
alles für…’
-
Erica Jong-
Melany, Bill, Sue, Kim, Stella, Pam, and Cobus Viljoen:
‘This world is not
respectable; it is mortal, tormented, confused, deluded forever; but it is
shot through with beauty, with love, with glints of courage and laughter;
and in these the spirit blooms timidly, and struggles to the light amid
the thorns.’
-
George Santayana-
John Weston, Bill Owen, Debbie Schroeder, and Helena Lombard: Thank you
for the language editing and sorting out my endless Microsoft word technical
conundrums.
De Wet and Carina: Thank you for your endless patience…
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University of Pretoria etd – Lombard, F D (2005)
UNIVERSITY OF PRETORIA
DEPARTMENT OF COMMUNICATION PATHOLOGY
Surname
Lombard
Initials
FD
Supervisor
Mr D Swanepoel
Co-supervisor
Carina Avenant
Date
February 2005
Title
An investigation of the Auditory P300 Event Related
Potential across gender
Abstract:
The P300 serves as a valuable tool in examining higher auditory functions such as auditory
attention and discrimination. Exploration of the P300 could be of value in a multi-lingual South
Africa where auditory processing evaluations still rely heavily on inappropriate linguistically
dependent tests. The P300 could potentially provide an objective, non-linguistically dependent
evaluation of auditory processing. The present study aimed to investigate the influences of
gender on the Auditory P300 Event Related Potential (AERP) and to contribute to establishing
a clinic-specific normative database. One hundred subjects (n=100) (50% male) with normal
hearing and no history of psychiatric illness were evaluated using the “odd-ball” paradigm.
The averages and ranges of the findings on latencies and amplitudes were reported. The
average latency values for the P300 were calculated at 314.7ms with a standard deviation of
37.2 ms. The average amplitude values were calculated at 7.1 µV with a standard deviation of
6.1 µV. No significant gender effect was found. In conclusion further research is
recommended to explore the clinical utility of the P300 in different age and gender groups,
using different protocols.
Opsomming:
Die doel van die huidige studie was ‘n ondersoek na die invloed van geslag op die ouditiewe
P300 en om ‘n bydrae te lewer in die samestelling van ‘n kliniek-spesifieke normatiewe
databasis. Hierdie metings is van belang aangesien dit ’n waardevolle instrument is vir die
evaluering van hoër ouditiewe funksies soos ouditiewe aandag en diskriminasie. Verdere
ondersoeke in die P300 kan van kliniese waarde wees in ‘n multi-linguistiese Suid-Afrika waar
evaluasies van ouditiewe prosessering steeds sterk leun op toetse wat linguisties afhanklik is
en dus ontoepaslik is. Die ouditiewe P300 kan ‘n objektiewe, nie-linguistiese metode bied om
ouditiewe prosessering te evalueer. Die studie het beoog om die effek van geslag op die
latentheid en amplitude van die betrokke potensiale te ondersoek. ’n Honderd proefpersone
(n=100)(50% manlik) met normale gehoor en geen geskiedenis van psigiatriese patologie nie,
is geëvalueer met behulp van die “odd-ball” paradigma. Die gemiddelde en totale reikwydte
van die latentheid en amplitude van elke potensiaal is opgeteken. Die gemiddelde latentheid
en amplitude was bereken as 314.7ms en 7.1µV onderskeidelik. Die standaard afwyking vir
die latenheid en amplitude was bereken as 37.2 ms en 6.1 µV. Geen betekenisvolle verskille
tussen mans en vrouens is waargeneem nie. Die gevolgtrekking van die studie was dat
verdere navorsing nodig is om die kliniese waarde van die P300 ten opsigte van verskillende
ouderdoms- en geslagsgroepe te ondersoek, met behulp van verskeie toetsprotokolle.
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Table of Contents
LIST OF TABLES .................................................................................................................................. VI
LIST OF FIGURES ...............................................................................................................................VII
LIST OF APPENDICES ..................................................................................................................... VIII
GLOSSARY AND ABBREVIATIONS................................................................................................ IX
1.
2.
BACKGROUND AND RATIONALE OF THE STUDY............................................................1
1.1.
INTRODUCTION ..........................................................................................................................1
1.2.
ORIENTATION ............................................................................................................................3
1.3.
RATIONALE ...............................................................................................................................6
1.4.
PROBLEM STATEMENT...............................................................................................................8
RESEARCH METHODOLOGY ...................................................................................................9
2.1.
INTRODUCTION ..........................................................................................................................9
2.2.
AIMS OF RESEARCH ................................................................................................................10
2.2.1.
Main Aim ...........................................................................................................................10
2.2.2.
Sub-aims ............................................................................................................................10
2.3.
RESEARCH DESIGN..................................................................................................................11
2.4.
SUBJECTS ................................................................................................................................12
2.4.1.
Selection Criteria...............................................................................................................12
2.4.2.
Selection procedures .........................................................................................................14
2.4.3.
Description of subjects ......................................................................................................15
2.5.
2.5.1.
Subject selection material and apparatus.........................................................................16
2.5.2.
Data collection material and apparatus ...........................................................................17
2.6.
PROCEDURE .............................................................................................................................17
2.6.1.
Data collection ..................................................................................................................18
2.6.2.
Stimulus parameters ..........................................................................................................19
2.6.3.
Recording parameters .......................................................................................................20
2.6.4.
Data analysis .....................................................................................................................20
2.6.5.
Data processing.................................................................................................................21
2.7.
3.
MATERIAL AND APPARATUS ...................................................................................................16
ETHICAL CONSIDERATIONS .....................................................................................................22
RESULTS AND DISCUSSION ....................................................................................................23
3.1.
AVERAGE LATENCIES AND AMPLITUDES OF THE AUDITORY P300 EVENT-RELATED POTENTIAL
……………………………………………………………………………………………..23
3.2.
THE VARIABILITY AND DISTRIBUTION OF LATENCIES AND AMPLITUDES OF THE AUDITORY
P300 EVOKED RESPONSE .......................................................................................................................30
3.3.
THE SIGNIFICANCE OF GENDER ...............................................................................................37
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3.4.
THE EFFECT OF THE ‘MARKING PROTOCOL’ ON THE RESULTING P300 LATENCIES AND
AMPLITUDES...........................................................................................................................................42
4.
CONCLUSION...............................................................................................................................45
4.1.
CRITICAL EVALUATION OF STUDY ..........................................................................................46
4.2.
RECOMMENDATIONS FOR FUTURE RESEARCH ........................................................................50
4.3.
A FINAL THOUGHT...................................................................................................................52
BIBLIOGRAPHY....................................................................................................................................53
APPENDIX A: CONSENT FORM........................................................................................................70
APPENDIX B: CASE HISTORY FORM.............................................................................................72
APPENDIX C: GRAPHIC ILLUSTRATION OF ALLR AND AERP ............................................74
APPENDIX D: EXAMPLE OF RESULTS ..........................................................................................75
APPENDIX E: RESULTS (RAW DATA) ............................................................................................76
P300 AMPLITUDE RAW DATA (µ V).........................................................................................................76
P300 SUBTRACTED WAVE AMPLITUDE RAW DATA (µ V)........................................................................78
P300 LATENCIES RAW DATA (MS) .........................................................................................................80
P300 SUBTRACTED WAVE LATENCIES RAW DATA (MS) .........................................................................82
APPENDIX F: AVERAGE LATENCIES AND AMPLITUDES FOR THE ALLR (P1, N1 AND
P2) ..............................................................................................................................................................84
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LIST OF TABLES
Table 2.1:
Stimulus parameters for recording of Auditory P300
19
Table 2.2:
Recording parameters for recording of the Auditory P300
20
Table 3.1:
Mean/Average values of the latencies and amplitudes of
24
ALLR’s and P300
Table 3.2:
Percentiles of the latencies and amplitudes of the P300 & 25
P300 (subtracted)
Table 3.3:
Mean P300 latencies and amplitudes reported by
28
different studies
Table 3.4:
p-values of the latencies and amplitudes of the P300 and
40
P300 Subtracted wave
Table 4.1:
Summary of average findings and range of P300 and
45
P300 Subtracted wave
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LIST OF FIGURES
Figure 2.1:
Female subject age distribution
15
Figure 2.2:
Male subject age distribution
16
Figure 3.1:
Age range of the different studies
27
Figure 3.2:
Findings on range of latencies for P1, N1, P2, P3 and
31
P3 Subtracted
Figure 3.3:
Findings on range of amplitudes for P1, N1, P2, P3 and 32
P3 Subtracted
Figure 3.4:
Comparison of the findings on the range of latencies of
33
the present study to Salamat & McPherson (1999) and
Theunissen (2002)
Figure 3.5:
Comparison of the findings on the range of amplitudes
34
of the present study to Salamat & McPherson (1999)
and Theunissen (2002)
Figure 3.6:
Gender differences for the P300 mean latencies
37
Figure 3.7:
Gender differences for the P300 Subtracted wave
38
mean latencies
Figure 3.8:
Gender differences for the P300 mean amplitudes
39
Figure 3.9:
Gender differences for the P300 Subtracted wave
39
mean amplitude
Figure 3.10:
Comparison between latencies for the P300 and the
43
P300 Subtracted wave
Figure 3.11:
Comparison between amplitudes for the P300 and the
43
P300 Subtracted wave
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LIST OF APPENDICES
Appendix A:
Consent Form
Appendix B:
Case History Form
Appendix C: Graphic illustration of ALLR and AERP
Appendix D: Example of results
Appendix E
Results (Raw data)
Appendix F
Average latencies and amplitudes for the ALLR (P1, N1 and
P2)
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Glossary and abbreviations
ABR: Auditory brainstem response. An evoked potential that occurs between
1ms and approximately 10ms post-stimulus. It is usually defined as having
five to seven prominent waves (peaks) labelled I through VII. Wave V is the
most robust and commonly used wave in the series (McPherson, 1996).
Active Electrode: Any signal occurring at this electrode will have a phase
inversion of 180. In EP recording from the scalp, the term active may be
misleading because all the electrodes across the scalp are considered active.
The preferred term would be inverting electrode (McPherson, 1996).
ADHD: Attention deficit and hyperactivity disorder (Bellis, 2003).
AEP: Auditory evoked potentials. A general term used to refer to any evoked
potential (EP) that is elicited using an auditory stimulus (McPherson, 1996).
Artefact: Any unwanted signal embedded in a recording that is not attributed
to the desired neural response (McPherson, 1996).
Attend condition: The observer is attending to the target stimulus and is
usually required to count or make some response (McPherson, 1996).
Behavioural response: Usually a verbal or motor response made by an
individual in response to a stimulus. An example would be locating a sound in
space or some other behaviour that is not a measurement of the biological
measure (McPherson, 1996).
CAPD: Central auditory processing disorder (Bellis, 2003)
Cognition: The process whereby an individual internalises some external
object or event (McPherson, 1996).
Common electrode: The relationship of one electrode to a second electrode;
usually refers to the non-inverting electrode (McPherson, 1996).
Common: This has two meanings in EP: (1) The relationship of one electrode
to a second electrode; usually refers to the non-inverting electrode; and (2) in
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ERP is a signal that occurs with a large probability than a target signal and is
generally to be ignored (McPherson, 1996).
Decay time: The amount of time it takes a gated signal to reach its minimum
(McPherson, 1996).
Emitted P300: A P300 response by the absence of a second stimulus in
paired stimulus paradigm when the subject has been instructed to ‘guess’ the
presence or absence of the second stimulus prior to the trial (McPherson,
1996).
Endogenous: Refers to the ERP generated by an internal response to the
external event and is usually due to perception or cognition. The nature of the
response changes according to the internalisation of the event, not the
dimension of the external event (McPherson, 1996).
EP: Evoked Potential. A series of electrical changes occurring in the
peripheral and central nervous system following stimulation of an endogenous
or peripheral nerve (McPherson, 1996).
ERP: Event-related potentials. An evoked potential elicited by an endogenous
stimulus representing higher level processing (i.e. cognition) (McPherson,
1996).
Event-related potential: see ERP.
Evoked Potential: see EP.
Exogenous: Refers to an EP generated by an external stimulus. The nature
of the response changes according to the dimensions of the external event
(McPherson, 1996).
Far-field: A far-field recording occurs when the recording electrode is situated
distally from the source (McPherson, 1996).
Microvolt: 10-6 volts. Abbreviated µV where 0.000001 volt equal 1µV
(McPherson, 1996).
Montage: The electrode positions used to record an EP. Usually referred to
the 10-20 international standard (Jasper, 1958).
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Morphology: The qualitative features of an evoked potential. It usually takes
into consideration the noisiness of the recording, the ‘smoothness’ of the
recording and how the recording appears relative to a textbook example, or at
least the ideal recording (McPherson, 1996).
Muscle artefact: Muscle potential that occurs to sensory stimulation or
random movement and in a time frame that overlaps the desired recorded EP
(see artefact)(McPherson, 1996).
N1: The first negative peak following the middle latency auditory evoked
potentials occurring between 80-150ms in adults (McPherson, 1996).
N100: See N1.
Non-inverting electrode: See Common electrode
P1: The first positive peak following the middle latency auditory evoked
potentials occurring between 55-80 ms in adults (also known as the P60)
(McPherson, 1996).
P2: The second positive peak following the middle latency auditory evoked
potentials or the first positive peak following the N100 and occurring between
145-180 ms in adults (also known as the P160) (McPherson, 1996).
P3: An endogenous event-related potential occurring between 220-380 ms in
adults (also known as P300). The P3 may have two subcomponents: (1) P3a
and (2) P3b (McPherson, 1996).
P300: See P3.
Perception: The process whereby an individual gathers information about
objects or events (McPherson, 1996).
Plateau time: The time a signal remains on its maximum intensity
(McPherson, 1996).
Rare signal: A target signal that occurs with a lesser probability than a
second signal. The subject is usually asked to respond when the signal occurs
(McPherson, 1996).
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Reference electrode: The relationship of one electrode to a second usually
refers to a common electrode (McPherson, 1996).
Sensation level: This is the intensity of a sound above or below an
individual’s own threshold. In some instances, the abbreviation has been
inappropriately used for a sound level referring to SPL (McPherson, 1996).
Sound pressure level: SPL. An absolute value measured in dB representing
the physical intensity of a sound (McPherson, 1996).
SPL: See sound pressure level.
Tone burst: Signals having a rise time, plateau time, and decay time of
sufficient duration to be perceived as having tonal information. In this
instance, tone would refer to a sinusoid or combination of sinusoids
(McPherson, 1996).
µV: See microvolt.
10-20 international system: A systematic standard for electrode location
(Jasper, 1958).
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1. Background and rationale of the study.
The aim of this chapter is to introduce the auditory P300 Event Related
Potential (AERP) and the problem that this study confronts, by providing the
rationale thereof, describing the terminology used and presenting an overview
of the content and organisation of the study.
1.1. Introduction
‘The greater the doubt the greater the awakening, the smaller the doubt the
smaller the awakening. No doubt, no awakening’ (Chang, 2003)
The P300 event related potential (ERP) has been shown to be a useful tool of
measurement both in the theoretical field of cognitive distance and clinically,
as a measure of central nervous system functioning (McPherson, 1996).
However, it has been shown to be easily influenced by both subject and
stimulus factors. If this is to become a recognised clinical tool, these effects
need to be quantified. The ERP is a relatively new tool in the advanced
audiological test battery, since its first classification in 1965 (Hall, 1992). It is a
differentially averaged, electrophysiological recorded signal which represents
the neurological produced electrical potentials, which occurs as the subject
mentally operates on a stimulus.
By definition, audiology is the science of hearing (Stach, 1998). Over the last
decades audiology has been evolving as an academic field of study, as well
as a clinical profession. The science of audiology includes the identification
and diagnosis of any hearing impairment and equally important, the
prevention and
management of the
disabilities caused by hearing
impairments. According to Katz (2001), the primary goal of a diagnostic
procedure is the successful rehabilitation of auditory impairment.
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Pure tone threshold audiometry is the standard behavioural procedure for
describing auditory sensitivity. The comparison of air- and bone-conduction
thresholds provides a fundamental index of auditory function for otological
diagnosis. Pure tone thresholds can thus be described as the cornerstone for
diagnostic procedures and rehabilitative planning (Yantis, 1994).
Throughout the advancement of audiology, a great deal of effort has been
invested in methods of determining hearing thresholds (the level at which
tones are perceived as barely audible) (Martin, 1997). To this day the pure
tone audiogram has served as the gold standard for various populations, but
despite its widely accepted value, it has some limitations. Assessment of
hearing by utilising pure tones provides valuable information regarding
sensitivity, but only limited information concerning receptive auditory
communication ability (Penrod, 1994). Auditory perception or speech
perception as we experience it daily occurs, for example, on a conversational
level. This phenomenon occurs on a supra-threshold level and not the
threshold levels determined by the pure tone audiogram (Penrod, 1994). The
pure tone audiogram provides valuable information with regard to the type,
degree and configuration of a hearing loss, but the standard audiogram is
insufficient for providing comprehensive diagnostic information regarding
supra-threshold processes such as auditory perception and attention
(Moncrieff & Jerger, 2000).
The need for supra-threshold evaluation procedures in the field of audiology
has caused an emphasis shift towards test procedures that can reach beyond
the peripheral hearing system to include processes such as auditory
perception (Jirsa, 2002). Despite many test procedures used to evaluate
auditory processing, there is still a great need for reliable procedures that
could objectively evaluate some of the conscious processes involved in
hearing (Bellis, 2003; Kraus, Burton Kock, McGee, Nicol & Cunningham,
1999; McFarland & Cacace, 1995; Hall, 1992).
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1.2. Orientation
Researchers from a number of disciplines have used electrophysiological
measures for years to evaluate aspects of the central nervous system (Hall,
1992). Until recently, audiologists have used electrophysiological measures
primarily for the evaluation of the peripheral auditory system. The diagnostic
usefulness of both the auditory brainstem response (ABR) and the middle
latency response (MLR) has been thoroughly documented (Goldstein &
Aldrich, 1999; Musiek, Baran & Pinheiro, 1994; Hall, 1992). In the last decade,
more audiologists have started to direct their efforts towards using
electrophysiological measures for to investigating and enhancing the
understanding of audition in the central nervous system (Jirsa, 2001; Jerger,
1998). Substantial evidence is accumulating pertaining to the clinical
relevance of a number of electrophysiological measures, including the P300
event-related potential (ERP) (Jirsa, 1992; Polich, 1998; Salamat &
McPherson, 1999; Kiehl, Laurens, Duty, Forster & Liddle, 2001; Yordanova,
Kolev & Polich, 2001).
The P300 is a far-field, differentially averaged electrophysiological recording
of the electrical activity of the cortex in response to the internalisation of an
auditory stimulus (Hall, 1992). It is an endogenous, or event related potential,
as the response is dependent on an internal cognitive “event” that is relatively
independent of stimulus features and subject characteristics (McPherson,
1996). The P300 auditory event-related potential (AERP) occurs between 300
to 700 ms (Jirsa & Clontz, 1990; Squires & Hecox, 1983), is a non-obligatory
waveform that is elicited using the “odd-ball” paradigm. This means one
stimulus is ‘common’ (frequent) and the other is odd (or infrequent). Generally
the “odd-ball” stimulus will be randomly present for 20% of the time. As the
P300 response is endogenous and dependent on the perceived difference
between two stimuli, the extent of the difference between the two types of
stimuli (i.e., frequent versus infrequent) will change the amplitude, latency and
morphology of the response (McPherson, 1996). It is also called the P300b to
separate it from an earlier occurring non-attentive waveform, often labelled the
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P300a (Kiehl et al., 2001) (see Appendix C: Graphic illustration of ALLR and
AERP).
The P300 matures later than the earlier waveforms such as the auditory
brainstem response (ABR). Several studies show a decrease in latency and
an increase in amplitude from the age of five through to the age of 16. This is
followed by a progressive decrease in amplitude and an increase in latency
throughout adulthood (Courchesne, 1978; Pfefferbaum, Ford, Roth & Kopell,
1980; Polich, Howard & Starr, 1985). The neural generator site for the P300
still raises great controversy because of the diffuse and complex nature of the
structures involved. Accumulative evidence suggests involvement of the
thalamus, inferior parietal lobe, temporal lobe, dorsolateral pre-frontal cortex,
cingulated cortex, amygdale and the hippocampus (Jirsa, 2002).
The P300 is not elicited passively, but requires the active participation of the
subject attending to specific stimuli in an on going train of standard stimuli
(Salamat & McPherson, 1999; McPherson, 1996). As active listener
participation is required to generate the P300 response it is widely accepted
as a physiological measure of cognitive processing (Hall, 1992). The P300
reflects processes related to attention, decision-making and memory updating
(McPherson, 1996). The P300 latency appears to be a function of stimulus
evaluation time which relates to the recognition and categorisation of a
stimulus (Alho, Sainio, Reinikainen & Naatanen, 1990), the speed of
information processing (Courchesne, 1978) and short-term working memory
processes (Yordanova et al, 2001). The P300 amplitude is related to the
subjective probability of the stimulus, stimulus meaning and information
processing (Johnson, 1986). It has been extensively used to evaluate various
aspects of psychophysiology, psychopathology and ageing (Pfefferbaum et
al., 1980; Polich et al., 1985; Ford, White & Csernansky, 1994). In general,
results have shown an increase in latency and a decrease in amplitude in the
clinical population (Jirsa, 2002). The P300 has also been used to investigate
various learning and developmental processes in children, as well as adults,
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including hyperactivity (Satterfield, Schell, Backs & Hidaka, 1984) and
language and motor speech disorders (Mason & Mellor, 1984).
The P300 response has also been investigated in children with Central
auditory processing disorders (CAPD). A significant relationship between
P300 results (amplitude and latencies) and deficits in selective attention,
short-term memory and auditory discrimination ability has been found in
children with confirmed CAPD (Jirsa & Clontz, 1990). The P300 has also
proved to be sensitive to behavioural changes resulting from therapeutic
programmes, and may be most useful in monitoring therapy progress (Jirsa,
1992).
Despite the continued success of the P300 AERP, the interpretation of its
waveforms remains debatable. Unlike the early auditory evoked potentials,
latency and amplitude values for the P300 are variable, even within a normal
population (Theunissen, 2002; McPherson, 1996; Hall, 1992). The P300 is
more diffuse than other long latency auditory evoked potentials, because of
the co-existing activity within the nervous system (McPherson, 1996). This
inherent variability makes the clinical application of P300 results in the time
domain difficult, even in experienced hands (Hall, 1992).
Due to its sensitivity to a great number of variables, including short-term
memory and attention (Polich, Howard, Starr, 1983; Hall and Mueller 1997),
the P300 has even less relevance for standard threshold seeking audiological
procedures as deficits in these areas will influence the results (Hall, 1992).
The science of audiology, however, encompasses substantially more than the
clinical estimation of hearing thresholds. The value of auditory late latency
responses exceeds the estimation of hearing thresholds (Kraus & McGee,
1994). What might present as a disadvantage in estimating hearing thresholds
therefore yields great possibilities for utilisation as a tool for assessing
processes that not only comprise an essential part of the hearing process, but
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University of Pretoria etd – Lombard, F D (2005)
also plays a vital role in normal cognitive function (Polich et al 1985; Jirsa,
2002).
1.3. Rationale
The use of event-related potentials (ERP’s) to identify pathological conditions
of the auditory system is complex. Developments in the field of ERP have
highlighted a more objective means of measuring a multitude of processes
involved in the complete hearing process (Hall & Mueller, 1997).The P300
offers great promise as a clinical tool in the identification of disorders in
cognitive functioning and auditory processing (Jirsa, 2002). However, it is
limited by the inherent variability of the response, even in normal subjects
(Hall and Mueller, 1992). Therefore it is of utmost importance to investigate
the variability of its characteristics in normal subjects, in order to identify an
abnormality accurately.
Unlike peripheral auditory evoked potentials such as the auditory brainstem
response which is very stable and has clearly specified parameters (Hall,
1992), the auditory event-related potentials are subject to significant variations
from both extrinsic and intrinsic factors. As a result of these variations,
establishing a normative database requires precise specifications of the
stimuli. These include recording conditions and environment, subject state
(including age, gender, various biological and psycho-physiological factors)
and response tasks (McPherson, 1996). Normative data has to be established
on each variable, whether on the subject (e.g. gender, age) or the
environment (e.g. stimulus, amplification).
In the auditory system, anatomic differences between males and females
have been found in the planum temporal, a supratemporal region of the
auditory association cortex (Kulynch, Vladar, Jones & Weinberger, 1994).
Both behavioural (Cohen, Levy & McShane, 1989; McGuinness & Pribram,
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1979; Rosenthal, Archer, Dimatteo, Koivumaki & Rogers, 1974) and
physiological auditory pathway asymmetries are known to exist between
gender in humans and animals (Ehret, 1987; Fitch, Brown, O’Conner & Tallal,
1993; King, Nicol, McGee & Krause, 1999). Hall (1992) does not consider
gender such a significant factor as age in P300 measurements. In 1986, John
Polich conducted a study showing no significant effect of gender on latencies
or amplitude (Polich, 1986). However other studies found larger P300
amplitude in adult females compared to adult males (Niwa & Hayashida,
1993). More recent studies have also shown that P300 latencies vary as a
function of age and gender (Ehlers, Wall, Garcia-Andrade & Phillips, 2001;
Gölgeli, S er, Ozesmi, Dolu, Ascioglu & Sahin, 1999; Bahramali, Gordon,
Lagopoulos, Lim, Li, Leslie & Wright, 1999). It is thus important to establish a
normative data base that encompasses the normal deviations of the P300.
The clinical definition of abnormality is based on the deviation from a mean
population value of two to three standard deviations (McPherson & Starr,
1993). Therefore, an understanding of P300 variations is important to
determine the limits of normal variations (Polich et al., 1985). Consequently, it
is not only essential to determine the average values and the characteristics
of the wave, but also the range and variability of these values within a normal
group of subjects pertaining to gender.
If audiologists are to be involved in the investigation and management of
hearing processes that reach beyond the peripheral hearing mechanism, but
nevertheless have a significant influence on an individuals’ auditory
functioning, it is unavoidable that they are informed about the nature of these
processes. As scientists we have an obligation towards research in this area.
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University of Pretoria etd – Lombard, F D (2005)
1.4. Problem statement
In an attempt to determine the validity of any diagnostic procedure, it is
necessary to establish the procedures’ ability to perform as intended (Roeser,
Valente & Hosford-Dunn, 2000). In the case of a P300 evoked response, it is
important to establish if P300 latencies and amplitudes vary as a function of
gender.
Preliminary studies (Theunissen, 2002; Ehlers et al., 2001; Gölgeli et al, 1999;
Bahramali, et al., 1999; Niwa & Hayashida, 1993) have shown significant
differences in latencies and amplitude values of the P300 response between
genders. The current research study aims to establish a gender-matched
normative database for the P300 auditory event-related potential. A recent
study conducted at the University of Pretoria, South Africa, found a great need
for further exploration on the effect of gender on the amplitude, and especially
on the latency of the P300 auditory event-related potential (Theunissen,
2002). It is clear that there is a need for clinic-specific norms for gender.
The problem statement can therefore be formulated as follows:
What is the gender matched norms for the P300 auditory event-related
potential at the Electrophysiology clinic at the Department of
Communication Pathology, University of Pretoria?
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University of Pretoria etd – Lombard, F D (2005)
2. Research Methodology
The research question underlying the current study has been discussed
extensively in Chapter 1. This chapter aims to describe the operational
method employed in this study. It is an attempt to validate the findings of the
current study and to encourage further research on the use of auditory P300
evoked responses, to assess neural processing of speech in individuals with
communication disorders.
2.1. Introduction
Although the word research strikes fear into the hearts of many audiologists
and speech-language therapists, it should be recognised that what many of us
do on a daily basis is, in essence, research (Bellis, 2003). According to
Silverman (1977) there should be no difference in the way we answer
clinically relevant questions, or test clinically relevant hypotheses for clinical or
research purposes.
Scientific research is distinguished from other research by the systematic
process of inquiry based on combined empirical and theoretical principles
(Graziano, 1993). Leedy (1997) refers to the research methodology simply as
an operational framework. Previous studies (Theunissen, 2002; Ehlers et al,.
2001; Gölgeli et al,. 1999; Bahramali et al., 1999; Niwa & Hayashida, 1993;
Martin et al., 1988) have shown significant gender differences in the latency
and amplitude values of the P300 auditory evoked potentials. In other studies,
no significant differences between values for different genders regarding the
P300 auditory evoked potentials were found (Polich, 1986; Hall, 1992;
McPherson, 1996). The need arises to determine if significant gender
differences exist, and to establish a normative data base, which can be used
to interpret P300 auditory evoked potential recordings. These findings should
also be validated as accurate and reliable.
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University of Pretoria etd – Lombard, F D (2005)
2.2. Aims of Research
The aims of the research project were the following:
2.2.1. Main Aim
The aim of this study was to determine the range of latency and amplitude
values for male and female subjects for the auditory P300 event- related
potential in a group of young adults in order to establish a gender specific
normative database.
The following sub-aims were formulated in order to realise the main aim of the
study:
2.2.2. Sub-aims
•
To determine the central tendencies (mean/average) of the
latencies and amplitudes of the auditory P300 event-related
potential.
•
To determine the normal variation (standard deviation) of the
auditory P300 event-related potential (latency and amplitude).
•
To establish whether there are any significant differences in male
and female subjects for the auditory P300 event-related potential
(latency and amplitude)
•
To determine whether using a subtraction protocol (subtracting the
common/frequent wave from the rare/infrequent wave to obtain a
‘derived’ P300) to mark the P300 results in a statistical difference
from marking the P300 on the rare/infrequent trace.
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University of Pretoria etd – Lombard, F D (2005)
2.3. Research Design
A descriptive, quantitative normative research design was selected (Thomas
& Nelson, 2001). Quantitative researchers seek to validate certain hypotheses
and generalise their findings to apply their new knowledge to other people and
situations (Leedy & Ormrod, 2001). This method generally applies objective
measurements and data is usually converted into numerical values and
statistics.
This method is the most applicable to the type of data required in this study.
Objective measurements were taken and the results were given in numerical
form (microvolt and milliseconds). The advantage of this method compared to
the qualitative method is that it is more focused, with known variables and
established guidelines, using deductive analysis, numbers and statistics
(Leedy & Ormrod, 2001). Electrophysiological measurements of the auditory
P300 event-related potential were used as the objective measurement (no
response required from the subject). This study specifically focused on the
morphological characteristics of the P300 wave, using the standard oddball
paradigm in a specific age group and the results are given in the numerical
values of these characteristics.
Controlled variables were identified as:
•
Age
•
Gender
•
Hearing level
•
Medication
•
Cognitive abilities
•
Cultural and logistical factors
•
Psychological disease
•
Subject’s state of wakefulness
The measured variables are the values of the P300 latencies and amplitudes
for each subject.
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University of Pretoria etd – Lombard, F D (2005)
2.4. Subjects
For this study 50 subjects (n=100) between the ages of 18 and 30 were
selected. All subjects were randomly selected.
2.4.1. Selection Criteria
Subjects were selected according to the following criteria:
(See Appendix B for Medical/Audiological History Questionnaire)
• Age
All subjects were between the ages of 18 and 30. According to the literature,
this age group is described as having the shortest P300 latencies (optimal
latencies) (Barajas, 1990). The latencies of the P300 decrease systematically
throughout childhood, reaching asymptote after puberty (Polich et al., 1985)
and waveforms generally do not reach adult values until the age of 17
(Buchwald, 1990).
• Gender
An equal distribution of gender was attempted (25 males and 25 females) so
results could be compared statistically. The participants were divided into two
groups according to gender.
• Hearing
Theoretically, there should be no direct effect of peripheral hearing loss on the
P300 (Musiek & Geurkink, 1981). However, P300 latency can be indirectly
affected by peripheral hearing loss, as N1 and P2 waves are often shifted in
latency (causing a shift in P300 latency) in the presence of a hearing loss
(Musiek &Lee, 1999). More recent studies have shown marked differences in
event-related potentials in conditions associated with poor speech perception
such as simulated hearing loss (Martin, Kurtzberg & Stapells, 1999; Martin,
Sigal, Kurtzberg &Stapells, 1997) and sensorineural hearing loss (Oates,
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University of Pretoria etd – Lombard, F D (2005)
Kurtzberg & Stapelles, 2002). For these reasons all subjects were required to
have normal hearing levels at 500, 1000 and 2000Hz as the frequent stimuli
are at 500Hz, and the infrequent stimuli at 2000Hz. Normal hearing in this
case was defined as pure tone air conduction thresholds between 0 and 15
dB (Hall & Mueller, 1997).
• Medication
No subjects on any medication, such as central nervous system or
psychotherapeutic drugs, which could have an effect on the P300 (Thomas,
Lacono, Bonanni, D’Andreamatteo & Onofrj, 2001; Polich & Kok, 1997), were
included in the study.
• Cognitive Abilities
The study required that all subjects, regardless of their age, should have
normal cognitive functioning, since the P300 is affected by general cognitive
functioning (McPherson, 1996). All the subjects were students or graduates
from a tertiary institution, and it was therefore presumed that they have normal
cognitive function.
• Other factors known to influence the P300
The test sample excluded subjects diagnosed with or suffering from the
following conditions known to affect P300 values:
•
Psychiatric disorders, such as depression and schizophrenia
(Vandoolaeghe, Van Hunsel, Nuyten & Maes, 1998; Wagner,
Roeschke, Fell & Frank, 1997),
•
Patients with organic mental disorders, such as epilepsy, head
injuries (Packard & Ham, 1996), dementia or stroke (Korpelainen,
Kauhanen,
Tolonen,
Brusin,
Mononen,
Hiltunin,
Sotaniemi,
Suominen & Myllyla, 2000; Yanai, Fujikawa, Osada & Yamawaki,
1997) and
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University of Pretoria etd – Lombard, F D (2005)
•
Subjects who suffer from alcoholism (Hada, Porjesz, Chorlian,
Begleiter & Polich, 2001).
2.4.2. Selection procedures
Non-probability sampling (Neuman, 1997) was used in the selection of
research subjects. These subjects were selected based on certain selection
criteria as well as availability (Time constraints of the research subjects).
Subjects had to comply with the selection criteria as stated in section 2.4.1.
The following procedures were used:
•
Subjects were approached personally, or by telephone, to
determine if they were available for testing.
•
Informed consent: All research subjects were briefed on the noninvasive nature of the procedure, the time involved in the execution
of the procedure, confidentiality as well as the objective of the
study. Furthermore, should they wish, all research subjects can
request a copy of the test results obtained. A letter of consent was
completed by each subject (See Appendix A).
•
Relevant audiological and medical information was collected using
an audiological case history form (Appendix B).
•
An otoscopic examination of the external meatus and tympanic
membrane was conducted to identify any possible pathology that
could cause conductive hearing loss. In order to pass the otoscopic
examination all subjects were required to have an identifiable light
reflex, while the position, colour and transparency of the tympanic
membrane were also taken into consideration (Hall & Mueller,
1997).
•
Pure tone air conduction audiometry was performed to determine
hearing thresholds at 500, 1000 and 2000 Hz for each subject. All
thresholds were required to fall within the normal range of hearing
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University of Pretoria etd – Lombard, F D (2005)
(0-15dB HL). A descending threshold-seeking procedure was used.
Testing was conducted in a soundproof room at the University of
Pretoria, which is routinely used for audiometric evaluations (Hall &
Mueller, 1997).
2.4.3. Description of subjects
Using the selection criteria and procedures as described above, 50 subjects
(50% male and 50% female) (n=100) were selected. All subjects were
between the ages of 18 and 30.
Female Subject Age Distribution
Age 29
12%
Age 30
8%
Age 18
12%
Age 19
8%
Age 27
4%
Age 22
4%
Age 26
12%
Age 25
4%
Age 23
20%
Age 24
16%
Figure 2.1: Female subject age distribution.
The mean age values for both male and female subjects were 24 years.
Figure 2.1 and 2.2 depicts the age distribution per gender.
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University of Pretoria etd – Lombard, F D (2005)
Male Subject Age distribution
Age 29
4%
Age 30
11%
Age 19
4%
Age 20
7%
Age 28
4%
Age 21
4%
Age 27
7%
Age 22
22%
Age 26
7%
Age 25
11%
Age 24
4%
Age 23
15%
Figure 2.2: Male subject age distribution.
All subjects were required to have hearing sensitivity within the normal range
(0-15 dB HL). The subjects were randomly selected with the notion to control
the extraneous variables through randomisation (Silverman, 1977).
2.5. Material and apparatus
2.5.1. Subject selection material and apparatus
•
Medical/audiological history questionnaire: This was initially
employed in the selection of participants for the study. The
questionnaire consisted of questions regarding previous hearing
history (hearing problems, noise exposure, and ototoxic drugs),
balance, tinnitus, current medication, psychiatric problems, organic
mental disorders and alcoholism. These questions were based on
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University of Pretoria etd – Lombard, F D (2005)
the subject selection criteria as stated earlier. An example of the
questionnaire used may be viewed in Appendix B.
•
Otoscopy: A Welch-Allyn otoscope was used for otoscopy.
•
Pure-tone Audiometry: Pure-tone thresholds at 500, 1000 and 2000
Hz were measured using the GSI-61 audiometer (calibrated on 10
February 2004 according to SABS requirements as stated in SABS
0154-1999). Telephonics TDH-49P earphones with MX 41/JR
cushioning were used. Testing was conducted in a single walled
soundproof booth.
2.5.2. Data collection material and apparatus
•
The auditory event-related potentials were recorded using a Biologic Navigator ‘E’ Version 5.63 module 317 computer.
•
Testing was conducted in a single-walled soundproof booth in a
sound-treated room.
•
Abrasive Skin Prepping Gel was used to clean the areas where
electrodes were placed in order to keep impedance values below
5k as this could affect results (Ferraro & Durrant, 1994).
•
EEG Conductive Electrode Gel was used for application of
electrodes.
•
Disc electrodes with a silver chloride surface connected to a BioLogic pre-amplifier were used for recordings.
•
Electrodes were attached to the specific areas using 3M Medipore
tape.
•
Etymotic Research ER-3A insert earphones with Earlink Eartips
were used to present the stimulus in the ear of the subject.
2.6. Procedure
One set of data was collected from each subject namely, auditory P300 eventrelated potentials. Data was collected at the Department of Communication
Pathology of the University of Pretoria.
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University of Pretoria etd – Lombard, F D (2005)
2.6.1. Data collection
•
Testing was conducted in a soundproof room at the University of
Pretoria routinely used for electrophysiological evaluations.
•
The skin of the subjects was cleaned using Abrasive Skin Prepping
Gel on the areas where the electrodes were placed.
•
EEG Conductive Electrode Gel was applied to each electrode
before attaching them to the specified sites (see Table 2.1 for
recording parameters).
•
After the electrodes were attached, subjects were instructed to lie
down comfortably in the supine position, but awake, as sleep
affects the amplitude of the P300 waveforms (Hall, 1992). Subjects
were instructed to lie as quietly as possible with their eyes closed to
minimise interference.
•
Subsequently, the subjects were instructed to count the infrequent
stimuli while lifting their forefingers slightly every time they heard
the infrequent stimulus. This ensured a recording of the P300 in the
active or attend state (Musiek & Lee, 1999; Mertens & Polich, 1997;
Lew & Polich, 1993).
•
After instructions were given, impedance testing was conducted to
determine whether the impedance values were below 5k
(Ferraro
& Durrant, 1994). If impedance values were too high, electrode
sites were cleaned again and electrodes reattached. This
procedure was repeated until the correct impedance values were
reached.
•
Following the impedance testing, the insert earphones were placed
in the subjects’ ears, after which the door to the soundproof room
was closed.
•
The recording of the P300 waveforms subsequently commenced.
Stimuli were presented through the insert earphones (See Table
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University of Pretoria etd – Lombard, F D (2005)
2.2 for stimulus parameters). This resulted in two traces per
recording, an ALLR (Auditory late latency response) from the
common stimuli and the auditory P300 from the rare stimuli.
Responses were averaged until a minimum of 25 infrequent stimuli
and 100 frequent stimuli were presented to limit testing time and
obtain a repeatable P300 waveform.
•
After the recording, results were printed.
2.6.2. Stimulus parameters
The stimulus parameters utilised to evoke the Auditory P300 can be viewed in
Table 2.1.
Table 2.1: Stimulus parameters for recording of Auditory P300.
Stimulus parameters
Rational
References
Musiek, Baran &
Pinheiro, 1994; Hall,
1992; Hall & Mueller,
1997; Nourse,2000;
Tremblay et al., 2003
Hall & Mueller, 1997;
Musiek et al., 1994;
Hall, 1992;
Stimulus
type
Tone burst
Facilitates use of frequencyspecific stimuli.
Stimulus
frequency
Frequent
(85%):500Hz
Infrequent
(15%):2000Hz
Facilitates frequency
discrimination task commonly
used for oddball paradigms.
May be varied as indicated.
Stimulus
intensity
70 dB nHL
High above threshold, as low
intensity stimuli may result in
smaller P3 amplitudes and
longer latencies.
Musiek et al., 1994;
Vesco et al., 1993
Rise and
fall time
10 ms
Plateau
time
20 ms
Stimulus
rate
1 tone every 0.8
sec
Optimal ALLR recordings
require rise and fall times of 10
ms or greater.
Optimal ALLR recordings
require rise and fall times of 10
ms or greater.
Onishi & Davis, 1968;
Hall & Mueller, 1997;
Tremblay et al., 2003
Onishi & Davis, 1968;
Hall & Mueller, 1997;
Tremblay et al., 2003
Musiek et al., 1994;
Hall & Mueller, 1997;
Tremblay et al., 2003
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University of Pretoria etd – Lombard, F D (2005)
2.6.3. Recording parameters
The parameters utilised in the recording of the Auditory P300 can be viewed
in Table 2.2.
Table 2.2: Recording parameters for recording of the Auditory P300.
Recording parameters
Rationale
References
Montage
Active electrodes:
Fz
Referenced at: M1,
M2
Ground Electrode:
FpZ
P300 reliably recorded
over frontal scalp area,
maximum amplitude
vertex.
Musiek & Lee, 1999; Hall,
1992; Hall & Mueller, 1997;
Wall et al., 1991; Jasper,
1958
Channels
Two
Facilitated by available
equipment.
Wall et al., 1991
Recording
strategy
Oddball paradigm
Provides a variety of
potentials (N1, P2 7 P300)
without additional time.
Chermak & Musiek, 1997;
Salamat & McPherson,
1999
Gain/Amp
lification
75 000
Response bigger than
ABR therefore less
amplification is needed.
Hall & Mueller, 1997;
Tremblay et al., 2003
Filters
High filter: 100 Hz
Sufficient to record low
frequency responses and
narrow enough to help
reduce interference
generated by muscle &
eye movements.
Harris & Hall, 1990; Hall &
Mueller, 1997; Tremblay et
al., 2003
Sufficient time to
accommodate P300
responses.
Musiek, Baran & Pinheiro,
1994; Hall & Mueller, 1997
Tremblay et al., 2003
Low filter: 1 Hz
Analysis
time
800ms
2.6.4. Data analysis
Descriptive statistics were obtained for each component of the P300 auditory
event-related potential. After the waveform was repeated, the P300 could be
identified as the largest positive peak. The P300 followed the N2 between 250
ms and 380 ms (Wilson, 2000) in the waveform resulting from the infrequent
stimulus. The P300 wave was marked in consultation with the research
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University of Pretoria etd – Lombard, F D (2005)
supervisor. If the wave was bifurcated the largest peak was marked as the
P300. If the wave appeared as a plateau, the point with the highest amplitude
was marked as the P300 (see Appendix D) (McPherson, 1996).
A ‘derived’ P300 was obtained by subtracting the common/frequent wave from
the rare/infrequent wave. On this derived trace the P300 was marked in the
usual manner as discussed above. The marked waveforms were printed for
further analysis.
Subsequently, the relevant information gathered from the printed data was
tabulated using Microsoft Excel spreadsheets. Relevant information consisted
of the latency (ms) and amplitude (µV) of each marked P300 waveform.
2.6.5. Data processing
To realise the sub-aims of the study, Microsoft Excel software was used to
obtain descriptive statistics of the data. All procedures were done using the
latency and amplitude values for the P300 recordings.
A univariate procedure was performed on every variable to determine:
•
the mean of each variable,
•
the standard deviation of each variable,
•
the minimum and maximum of each variable and
•
the percentiles of each variable.
The mean value of the amplitude and latencies was further analysed by
utilising a non-parametric test, the Wilcoxon Rank Sum Test, to establish
whether statistical differences existed between genders for the P300 AERP.
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2.7. Ethical considerations
The explosion of biomedical and behavioural research in the last half of the
twentieth century has bought about scrutiny of the ethical principles by which
investigators should be guided.
The Belmont Report of the National
Commission for the Protection of Human Subjects Of Biomedical and
Behavioural research, released in 1979, describes three basic ethical
principles that should guide researchers. The first of principle is respect for
persons, this signifies that the choice of autonomous persons must be
respected and those with diminished autonomy should be protected. The
Second principle is that of beneficence which implies an obligation to secure
the well being of persons by not harming them and by maximizing the benefitto-risk ratio. The third principle is justice meaning equality in the sharing of the
risks and benefits. Many academic institutions cite the Belmont Report as the
ethical standard to be applied before approving research under their
jurisdiction. Internationally the Declaration of Helsinki is often the standard by
which human subjects research is judged, although it is specific to medical as
opposed to behavioural, research (Sininger, Chair, Marsh, Walden & Wilber,
2003).
Ethical clearance for this research study was obtained from the Ethics
Committee of the University of Pretoria. Informed consent was obtained from
each subject. Subjects were fully informed about the test procedures. They
were made aware of their right to ask and have questions answered as well
as their right to withdraw consent at any time. Participants were informed that
data gathered during this study will be used for research purposes only (Letter
of Consent: Appendix A).
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3. Results and Discussion
The aim of this study was to determine the range of latency and amplitude
values for male and female subjects for the auditory P300 event- related
potential in a group of young adults and consequently to establish a gender
specific normative database.
The results obtained will be discussed in the following section according to the
sub-aims formulated in paragraph 2.2 of the methodology.
3.1. Average latencies and amplitudes of the
auditory P300 event-related potential
The first sub-aim was to determine the central tendencies (average) of the
latencies and amplitudes of the auditory P300 event-related potential.
The mean or average (sum of the measurements divided by the total number
of measurements) (Ott & Mendenhall, 1994) of the latencies and amplitude of
each data point is depicted in Table 3.1. The complete set of results with the
latency and amplitude of the P300 as determined for each subject is
represented in Appendix E. The average value of each variable is included in
the results as this value is intended to represent “the best guess as to what is
most characteristic of the total population” (Leedy & Ormond, 2001:268) and
therefore comprises an essential part of the normative database.
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University of Pretoria etd – Lombard, F D (2005)
Table 3.1 Mean/Average values of the latencies and amplitudes of ALLRs
& P300.
Mean
Standard deviation
Latency (in ms)
89.9
29.5
Amplitude (in µV)
1.6
1.3
Latency (in ms)
121.9
38.3
Amplitude (in µV)
-3.0
3.8
Latency (in ms)
188.3
34.02
Amplitude (in µV)
3.5
5.7
Latency (in ms)
314.7
37.2
Amplitude (in µV)
7.1
6.1
P300
Latency (in ms)
309.9
34.6
(Subtracted)
Amplitude (in µV)
6.9
6.5
Variable
P100
N100
P200
P300
The average or mean P300 latency was established at 314.7 ms and 309.9
ms for the P300 subtracted wave. The amplitude measurements resulted in
an average of 7.1 µV for the P300 wave and 6.1 µV for the P300 subtracted
wave.
One disadvantage of using the mean is that it is sensitive to extreme values
(Keller & Warrack, 2000). The median is a measure of central location which
is not sensitive to extreme values. The median (50th percentile) (Table 3.2)
latency values for the P300 and the P300 subtracted wave were 311.7ms and
305.5ms respectively. The median (50th percentile) amplitude values were
calculated as 5.93µV and 4.85µV for the P300 and P300 subtracted
respectively.
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University of Pretoria etd – Lombard, F D (2005)
Table 3.2: Percentiles of the latencies and amplitudes of the P300 & P300
(subtracted).
25th
Variable
Median
Percentile
75th
IQR (inter
Percentile
quartile
range)
Latency (in ms)
287.48
311.7
342.17
54.69
Amplitude (in µV)
2.28
4.54
9.69
7.42
P300
Latency (in ms)
286.7
305.45
331.33
44.63
Subtracted
Amplitude (in µV)
2.6
4.85
9.41
6.81
P300
The P300 peak was generally less precise in its repeatability than N100 and
P200 and often required more than two recordings to obtain sufficient
repetition. According to Wilson (2000) and Hall (1992), the ALLR and P300
show much greater variability than the ABR and the rules of repeatability do
not strictly apply. Considering this statement, the reliability of the results is not
significantly affected by the reduced repeatability.
Substantial research on the clinical value of the P300 in various fields has
accumulated extensive literature on the expected values for P300 latencies
and amplitudes. These fields include: Electrophysiological evaluation of
auditory processing (Hall & Mueller, 1997), studies of various cognitive
processes (Yamaguchi & Knight, 1991; McPherson, 1996), ageing (Goodin et
al., 1978; Barajas, 1990; Coyle et al., 1991; Garcia de la Cadena et al., 1996;
Kuegler, 1997) and a variety of different mental illnesses (Hada et al., 2001;
Vandoolaeghe et al., 1998).
The findings in the current research can be related to a number of studies
found in the literature. Differences in test protocols were apparent when
comparing the studies, for instance:
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University of Pretoria etd – Lombard, F D (2005)
•
Electrode placements were different in virtually every study, depending
on the facilities available and the preferences of the examiner. Nourse
(2000), for example, used a one-channel recording with a single active
electrode at Fz (high forehead), while Michalewski et al. (1982)
recorded the P300 from three different active electrodes (mounted at
Fz, Cz, and Pz). Anderer, Heibert and Semlitsch (1996) similarly
reported separate findings for Fz, Cz and Pz. Bourtros et al. (1997)
recorded P300s from Pz. Polich, Howard and Starr (1985) recorded
responses from the vertex (Cz) site only and Picton et al. (1984)
recorded from temporal, parietal, frontal and vertex sites. Salamat and
McPherson (1999) recorded responses three times from 22 electrode
sites. Wall et al. (1991) and Theunissen (2002) recorded the P300
response with active electrodes at Cz and Fz, similar to the present
study.
•
Stimulus parameters, such as stimulus intensity and interstimulus
intervals varied greatly. Nourse (2000) experimented with three
different protocols by altering the intensity values of the infrequent
stimuli (using 25, 22 and 21 dBSL respectively). Michalewski et al.
(1982) presented stimuli at 60 dBSL (similar to the present study),
while Anderer et al. (1996) used a higher intensity of 90 dB SPL,
identical to that of Picton et al. (1984) and similar to that of Boutros et
al. (1997) who presented tones at 95 dB SPL. Salamat and McPherson
(1999) recorded the P300 using three different interstimulus intervals.
Wall et al. (1991) presented stimuli at an intensity of 85 dB nHL.
•
Separate studies also showed differences in performance tasks
required from subjects. Nourse (2000) and Polich, Howard and Starr
(1985) used a frequency discrimination task (Oddball Paradigm,
matching that of the present study), as did Picton et al. (1984), Boutros
et al. (1997) and Theunissen (2002). Anderer et al. (1996) required an
intensity discrimination task, while Michalewski et al (1982) instructed
subjects to count omitted clicks (in other words discriminate between
presence and absence of stimuli). Salamat and McPherson (1999)
used a continuous performance task which required the subjects to
26
University of Pretoria etd – Lombard, F D (2005)
respond to frequent stimuli and refrain from responding to the
infrequent stimuli.
•
Selection criteria differed across studies, for instance in terms of age, a
variable that has been established as a significantly influential factor
(Hall, 1992). The different age groups of the different studies are
depicted in Figure 3.1.
Age ranges of diffrent studies
9
20
8
20
10
Number of study
7
68
59
19
18
12
5
19
10
17
30
29
8
25
25
3
19
6
2
18
6
1
18
5
0
20
79
29
6
4
88
1. Nourse (2000)
2. Theunissen (2002)
3. Wall et al. (1991)
4. Salamat & McPherson (1999)
5. Michalewski et al. (1982)
6. Present study
7. Polich et al. (1985)
8. Picton et al. (1984)
9. Anderer et al. (1997)
24
23
40
60
80
100
120
140
160
180
Age (in years)
Figure 3.1: Age range of the different studies.
An additional study will be referred to (Boutros et al., 1997), which only
reported the average age of the subjects (29.8 years). Although Anderer et al.
(1996) used subjects from the greatest range of ages, they separately
reported on findings in different age groups (e.g. 10-19 years; 20-29 years
etc.). When referring to this study, the findings for the age group 20-29 years
will be used. The results of the relevant studies are indicated in Table 3.3.
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University of Pretoria etd – Lombard, F D (2005)
Table 3.3: Mean P300 latencies and amplitudes reported by different studies.
N
STUDY
Age
Mean
Mean
Range
Latency
Amplitude
P300
100
18-30
314.7 ms
7.1 µV
P300
100
18-30
309.9 ms
6.9 µV
Theunissen (2002)
24
18-24
317.79 ms
9.58 µV
Nourse
20
18-23
303.1 ms
Absolute
values not
reported
Present
Subtracted
332.2 ms
(2000)
319.1 ms
Michalewski et al.
(1982)
5
19-26
412.3 ms (Fz)
407.8 ms (Cz)
Absolute
values not
reported
439.8 ms (Pz)
Anderer et al.
58
20-29
(1997)
Boutros et al.
40
72
20-79
(1984)
Salamat & McPherson
355 ms (Cz)
15.9 µV (Cz)
361 ms (Pz)
19.5 µV (Pz)
328 ms
6.7 µV
350 ms
11.8 µV
366 ms
8.2 µV
377 ms
8.5 µV
18
20-29
287 ms
18
20-29
287 ms
20
17-25
353.5 ms
17.9 µV
372 ms
16.1 µV
387.6 ms
15.68 µV
289 ms
13.2 µV
(1999)
Wall et al,
8.8 µV (Fz)
29.8
(1997)
Picton et al.
Mean age:
353 ms (Fz)
17
19-25
1991
28
University of Pretoria etd – Lombard, F D (2005)
The latencies reported by Theunissen (2002), Nourse (2000) and Boutros et
al. (1997) were all within 20 ms or closer to the present study’s latencies for
the P300 and the P300 subtracted wave. The latencies reported by Polich et
al. (1985) for subjects between 10 and 19 years also showed a close
resemblance, probably due to the proximity of the age group.
The latency values reported by Anderer et al. (1997), Picton et al. (1984) and
Salamat and McPherson (1999) were relatively close to 360 ms (ranging from
350 ms to 387 ms). These values are about 40 ms above those reported in
the present study, but are still within the normal range as defined by Wilson
(2000). The latency values noted by Wall et al. (1991) were about 30 ms
smaller than those generated by the present study but still within the normal
range (Wilson, 2000).
The latency values reported by Michalewski et al. (1982) were approximately
100 ms higher than those of the present study and four other studies (Nourse,
2000; Boutros et al., 1997; Polich et al., 1985). None of the values reported by
Michalewski et al. (1982) fell within the normal range for evoked responses as
defined by Musiek et al. (1994) and Wilson (2000). The large differences in
results may be explained in terms of the test protocol. Michalewski and
colleagues (1982) used a test protocol with significant differences to the other
studies. Their aim was to measure emitted responses (potentials that need
not be elicited using a physical stimulus) versus the evoked responses
gathered in the other studies. This meant that they only used click stimuli, and
subjects were required to count omitted clicks, in contrast with the frequency
discrimination task used in the other studies. Although these two performance
tasks seem similar, it made use of the actual absence of stimuli to elicit the
auditory P300 responses, as no stimulus is needed to elicit an omitted
potential. This protocol eliminates the effect of sensory neural hearing loss
that could indirectly influence the results (Michalewski et al., 1982). Average
amplitude findings reported in the encountered literature were relatively
29
University of Pretoria etd – Lombard, F D (2005)
equivalent to those reported in this study, varying between 3.6µV (Nourse,
2000) and 19.5 µV (Anderer et al., 1996).
The need for a clinic-specific normative database arises if the researcher is to
reduce the number of variables that might affect the results (Hall, 2000). One
of the objectives of the present study was to initiate the start of a clinic-specific
normative data base. Latency and amplitude values of the present study
compare favourably with results obtained by Theunissen (2002). Latency
values for the P300 in both studies showed a difference of 3 ms and
amplitude values showed a difference of 2 µV. These differences validate the
reliability of the values obtained in the present study. A clinic-specific
normative data base will enable future examiners to compare clinical findings
to normative data obtained using the same protocol (Hall, 2000).
3.2. The variability and distribution of latencies
and amplitudes of the auditory P300
evoked response
The second sub-aim was to determine the normal variation of the auditory
P300 cortical evoked response.
A variety of calculations were executed to render a representation of the
distribution and range of variability of all the data. The following descriptive
statistics of each variable (P300 latencies and amplitudes and, in addition,
also the latency and amplitude values of the ALLR’s namely P100, N100 and
P200) were provided:
•
The minimum and maximum values and
•
The standard deviation
30
University of Pretoria etd – Lombard, F D (2005)
•
Percentiles
A visual presentation of the distribution (variability) of the latencies and
amplitudes of the P300, P300 subtracted wave, P100, N100 and P200 can be
seen in Figure 3.2 and 3.3.
Responses
Range of Latencies (in ms)
P1
39.83
N1
49.2
107.24
134.37
121.07
P2
147.07
183.57
125
246.07
P3 (Sub)
230.45
165.61
396.08
P3
227.32
169.63
396.95
0
100
200
300
400
500
600
700
800
Latencies(in ms)
Figure 3.2: Findings on range of latencies for P1, N1, P2, P3 and P3
(Subtracted).
Figure 3.2 illustrates the minimum and maximum values of the P300 latency,
found respectively at 227.32 ms and 396.95 ms. This indicates a range of
about 169.63 ms. The P300 subtracted wave showed similar values with
minimum and maximum values of 230.45 ms and 396.08 ms respectively,
indicating a range of 165.61 ms. These ranges were larger than those
reported for the P1, N1 and P2.
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University of Pretoria etd – Lombard, F D (2005)
Response
Range of amplitudes (In uV)
P1
0.02
N1
-9.09
P2
4.13
24.71
-3.1
P3 (Sub)
0.01
P3
0.08
-10
4.15
0
15.62
37.46
34.36
41.23
41.24
37.51
10
20
37.59
30
40
50
60
70
80
90
Amplitude (uV)
Figure 3.3: Findings on range of amplitudes for P1, N1, P2, P3 and P3
(Subtracted).
The range of amplitudes for the P300 was between 0.08 µV and 37.59 µV (a
total range of 37.51 µV) and for the P300 subtracted wave was between 0.01
µV and 41.24 µV (a total range of 41.23). These values once again showed
greater variability than those for P1, N1 and P2 values. These discrepancies
are demonstrated by figures 3.2 and 3.3 and confirmed by the standard
deviation values shown in Table 3.1.
The literature generally describes the P300 response as a large, positive
wave occurring at approximately 300 ms after a rare or infrequent stimulus
(Hall & Mueller, 1997; Musiek & Lee, 1999). Musiek et al (1994) describe
abnormal P300 latencies as later than 350 ms, while Wilson (2000) estimates
that latencies in normal adults should be between 250 and 380 ms. The
present study recorded responses, which occurred after 350 ms in 19 normal
adults tested (the maximum latency recorded at 396.95 ms). These findings
suggest the guidelines provided by Wilson (2000) might be more appropriate
for the clinical setting described in this study. In terms of amplitude, the
32
University of Pretoria etd – Lombard, F D (2005)
standard deviation of 6.1 µV (6.5µV for the P300 subtracted) is similar to that
of the 7 µV reported by Wall et al. (1991). These values also compare
favourably with the values reported by Salamat and McPherson (1999)
(between 3.9 µV and 5 µV), Anderer et al. (1996) (values between 5.4 µV and
6.2 µV) and Theunissen (2002) (3.6 µV).
Salamat and McPherson (1999), using a continuous performance task,
reported the range of P300 latencies and amplitudes for three different
interstimulus intervals. Theunissen (2002) used the oddball paradigm and
utilised the same test protocol as the present study. Once again, the
differences and similarities in test protocols must be considered when
comparing these findings to that of the present study (see section 3.1 above
for a more detailed description of these two studies). A comparison of their
findings with those of the present study is illustrated in Figure 3.4 (latency)
and Figure 3.5 (amplitude).
Range of latencies (in ms)
293
Number of study
6
187
5
318
95
4
318
86
258
3
480
413
404
110
368
2
230
166
396
1
227
169
396
0
100
200
300
400
500
600
1. Present study P300
2. Present study P300 subtracted wave
3. Theunissen (2002)
4. Salamat & McPherson (1999) –
interstimulus interval (ISI) 1
5. Salamat & McPherson (1999) – ISI 2
6. Salamat & McPherson (1999) – ISI 3
700
800
900
1000
Latency (in ms)
Figure 3.4: Comparison of the findings on the range of latencies of the
present study to Salamat & McPherson (1999) and Theunissen (2002).
33
University of Pretoria etd – Lombard, F D (2005)
Figure 3.4 indicates that latencies reported in the present study are very
similar to that of Salamat and McPherson (1999) and Theunissen (2002) in
terms of range. Although there are differences in the absolute minimum and
maximum latency values, there is a marked correspondence in terms of the
size of the range of latencies.
Number of study
Range of amplitudes
6
9.3
5
9.9
17.9
27.8
4
11.2
16.3
27.5
2
3
15.6
16.3
2 0.01
1. Present study P300
2. Present study P300 subtracted wave
3. Theunissen (2002)
4. Salamat & McPherson (1999) –
41.24 interstimulus interval (ISI) 1
5. Salamat & McPherson (1999) – ISI 2
6. Salamat & McPherson (1999) – ISI 3
18.3
41.23
1 0.08
0
24.9
37.51
10
20
37.59
30
40
50
60
70
80
90
Amplitude (in uV)
Figure 3.5: Comparison of the findings on the range of amplitudes of the
present study to Salamat & McPherson (1999) and Theunissen (2002).
Figure 3.5 indicates a larger range of amplitude values in the present study
than that found in the studies of Salamat and McPherson (1999) and
Theunissen (2002). The minimum values of 0.01 and 0.08 for the P300 and
the P300 subtracted wave respectively, were obtained by only two of the
normal adults tested (n=100), thus only 2% of the total test population.
Considering this, it can be said that comparing minimum and maximum values
may be misleading. The standard deviation can be more useful to interpret
these values. The standard deviation values of the present study were 6 µV
for both the P300 and the P300 Subtracted wave. Theunissen (2002) reported
a standard deviation value of 4µV.
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University of Pretoria etd – Lombard, F D (2005)
Measures of relative standing (percentiles) can also be used to describe the
shape of the distribution (Keller and Warrack, 2000). The advantage of this
method is that it is not sensitive to extreme values and eliminates outliers (see
Table 3.2). The P300 latencies presented with a range of values from the 25th
percentile (first quartile) to 75th percentile (third quartile) of 287.48 ms to
342.17 compared to the P300 (subtracted) latencies range of 286.7 ms to
331.33 ms. The 25th percentile to 75th percentile value range for the P300
amplitudes were 2.28 µV to 9.69 µV compared to the P300 (subtracted)
amplitude range of 2.6 µV to 9.41 µV.
This notable variability of the P300 waveform when compared to the P100,
N100 and P200 can partially be explained by the very nature of the response.
The P300 is described as an endogenous response dependent on subject
factors such as attention (Hall, 1992), rather than being directly influenced by
stimulus factors. The attention factors are, however, closely related to
stimulus factors (Hall, 1992) such as rate, frequency and task complexity.
These are factors that often vary from one clinical setting to another, creating
remarkable discrepancies between test findings of different researchers (see
Table 3.3).
In addition to the variance in the findings of different researchers, there is
great inter-subject variability within this study in terms of latency and
amplitude. Since the study is limited by age, gender and drugs and used the
same stimulus and recording parameters for every subject, these differences
need to be further investigated. The very nature of the P300 as an
endogenous response dependent on subject factors such as attention, results
in inter-subject variability, as the particular cognitive process required to
create the response may vary, even within a normal population. Beydagi et al.
(2000) investigated the correlation between working memory and the eventrelated potential in healthy subjects and found that variations in the recall time
of the subjects yielded differences in P300 latencies. Motivation, personality
and a number of other factors (briefly discussed below) may also influence the
35
University of Pretoria etd – Lombard, F D (2005)
P300 responses (Hall, 1992). An example is the psychological state of the
subject (Musiek, Verkest & Gollegly, 1988). The present study is controlled for
the presence of serious psychiatric illness in the selection criteria, but the
exact state of mind of each subject was not evaluated prior to testing. The
personality of a subject might also influence the P300. Vedeniapin et al.
(2001) examined the relation between self-directedness, as a personality trait
and the P300 response, and concluded that subjects with a low score on the
self-directedness scale of the Temperament and Character Inventory had
significant reduced P300 responses. Hostility and aggression can also have
an effect on the P300, as illustrated in a study by Bond and Surguy (2000),
who studied the effect of aggression in a normal population on P300
components. They found significant prolonged P300 latencies in more hostile
or aggressive subjects.
These findings indicate that there are a great number of personal
characteristics and psychological factors that might influence the P300 results.
This may also give some explanation of the great inter-subject variability for
the P300 response, even within a group of normal adult subjects. The clinical
utility of the auditory P300 as a valid diagnostic measure in clinical audiology,
however, remains questionable. It is self-evident that audiologists will not
always be able to control these factors when using event-related potentials in
the clinical setting. However, if a recorded sample can be compared to a
clinic-specific normative database, it may serve as a useful tool as part of a
test battery. It is important though, that the examiner takes an acceptable
degree of variability into account.
The scope of this study did not include an investigation of the Auditory Late
Latency Responses (ALLR). Due to the nature of recording technique involved
in recording the Auditory P300, these values where available. The average
latencies and amplitudes for ALLR’s (P1, N1, and P2) can be seen in
Appendix F in graphic format.
36
University of Pretoria etd – Lombard, F D (2005)
3.3. The Significance of gender
The third sub-aim was to establish if there are statistically significant
differences between male and female subjects using the auditory P300 event
related potentials (latency and amplitudes).
The mean latencies and amplitudes (P300 and P300 subtracted wave) as
calculated separately for males and females are depicted below in Figure 3.6,
3.7, 3.8 and 3.9. After calculating the mean values for each group, the
Wilcoxon Rank Sum test was performed to determine whether there is a
statistically significant difference between each group for each variable (P300
& P300 subtracted wave latencies and amplitudes). This analysis gives a pvalue which indicates the probability that the differences are not due to
chance factors alone (Keller & Warrack, 2000).
P300 Latencies
350
314.6
314.8
314.7
300
Latency (in ms)
250
200
Female
Male
150
Total
100
40.3
34.2
37.2
50
0
Mean
Standerd Deviation
Female
314.6
34.2
Male
314.8
40.3
Total
314.7
37.2
Figure 3.6: Gender differences for the P300 mean latencies.
37
University of Pretoria etd – Lombard, F D (2005)
P300 Subtracted wave Latencies
350
306.4
313.4
309.9
300
250
200
Latency (in ms)
Female
Male
150
Total
100
34.5
34.6
34.6
50
0
Mean
Standard Deviation
Female
306.4
34.5
Male
313.4
34.6
Total
309.9
34.6
Figure 3.7: Gender differences for the P300 subtracted wave mean
latencies.
Figure 3.6 and Figure 3.7 indicates the latency values for the P300 and P300
subtracted wave. No significant differences are indicated for either the female
or male latencies. Standard deviations (also seen in Figure 3.6 & 3.7) for both
female and male subjects showed only marginal differences. No significant
effects of gender were observed for the latency of the P300 and P300
subtracted wave (p < 0.05). The p-values are indicated in Table 3.4.
38
University of Pretoria etd – Lombard, F D (2005)
P300 Amplitudes
7.6
7.6
7.4
7.1
Amplitude (in uV)
7.2
7
6.7
6.7
6.8
6.6
6.6
Female
6.4
Male
Total
6.4
6.2
6
5.8
Mean
Standard Deviation
Female
7.6
6.4
Male
6.7
6.7
Total
7.1
6.6
Figure 3.8: Gender differences for the P300 mean amplitudes.
P300 Subtracted wave Amplitudes
8
7.03
6.8
7.2
6.9
6.5
7
5.8
Amplitude (in uV)
6
5
4
Female
Male
3
Total
2
1
0
Mean
Standard Deviation
Female
6.8
5.8
Male
7.03
7.2
Total
6.9
6.5
Figure 3.9: Gender differences for the P300 subtracted wave mean
amplitudes.
Figure 3.8 and 3.9 indicates the amplitude values for the P300 and P300
subtracted wave. The amplitude values for the female subjects show larger
P300 amplitudes (Figure 3.8). Interestingly, the female amplitude values for
39
University of Pretoria etd – Lombard, F D (2005)
the P300 subtracted wave show only a marginal difference from the male
amplitude values (Figure 3.9). The standard deviation for both male and
female subjects shows only marginal differences. Statistically, no significant
difference was found for the amplitude values for male and female subjects
(see Table 3.4 for p-values). No significant effect on gender was observed for
the amplitude values of the P300 and P300 subtracted wave.
Table 3.4: p-values of the latencies and amplitudes of the P300 and P300
Subtracted wave.
p-value
Variable
Statistically
significant?
(p< 0.05)
P300
P300
Latency
0.75
No
Amplitude
0.35
No
Latency
0.22
No
Amplitude
0.99
No
Subtracted
Wave
When examining the literature on the subject of gender effects on the P300, it
becomes clear that this particular variable has rarely been investigated (Hall,
1992). However, some authors have reported a gender effect for one or more
of the late responses. Hoffman & Polich (1999) reported that the P300
response tends to be larger in females than in males. Similar results were
40
University of Pretoria etd – Lombard, F D (2005)
found by Niwa and Hayashida (1993) and Hirayasu et al. (2000), who found
larger P300 amplitudes in adult females compared to males. Other studies
have also shown that P300 latencies vary as a function of age and gender
(Ehlers, Wall, Garcia-Andrade & Phillips, 2001; Gölgeli, S er, Ozesmi, Dolu,
Ascioglu & Sahin, 1999; Bahramali, Gordon, Lagopoulos, Lim, Li, Leslie &
Wright, 1999). However, Polich (1986), who examined the normal variation of
the P300, found no significant differences in either latency or amplitude
between males and females. Similarly, Hall (1992) and McPherson (1996) feel
gender is not such a significant factor in P300 measurements as age.
The present study found marginal differences in latency and amplitude values
for the P300 with female latencies shorter and amplitudes higher than that of
their male counterparts. None of these differences were statistically
significant.
The study done by Theunissen (2002) utilising the same test
protocol, yielded similar results.
According to Friedman et al. (1985), gender differences might be due to
variations in processing strategies between males and females. Others
attribute these differences to structural anatomic diversities between males
and females (Steinmetz et al., 1995; Witelson & Kigar, 1992). A number of
other studies mentioning gender effects on the P300 primarily focused on
either the effect of ageing or the interaction between age and gender (Ehlers
et al., 2001; Hirayasu et al., 2000; Gölgeli et al., 1999; Bahramali et al., 1999;
Kugler et al., 1996; Kugler, 1996; Segalowitz & Barnes, 1993; Yamashita et
al., 1991). Segalowitz and Barnes (1993) for instance, reported larger P300
amplitudes in females than in males in a young adolescent group, while in the
older adolescent group (17 years), the males presented with larger
amplitudes. The discrepancy in these findings is attributed to the differences
in the maturity rate between males and females (Van Beijsterveldt et al.,
1998). The present study did not explore this relationship as it controlled the
age group of the subjects.
41
University of Pretoria etd – Lombard, F D (2005)
From the empirical evidence in this study, it is clear there is a need for further
investigation into the interaction and effect of age and gender on the P300
response. The findings of such research can be utilised to build and
strengthen a clinic-specific normative database and clarify the controversies
around these variables, which could possibly influence clinical results.
3.4. The effect of the ‘marking protocol’ on the
resulting P300 latencies and amplitudes
The last sub-aim was to determine if using a subtraction protocol (subtracting
the common/frequent wave from the rare/infrequent wave to obtain a ‘derived’
P300) to mark the P300 has a statistical difference from marking the P300 on
the rare/infrequent wave.
There are currently two different methods of marking and interpreting the
resulting P300 response. The first is to mark the P300 as the largest positive
response between 250 ms and 380 ms post stimulus on the infrequent or rare
wave form (McPherson, 1996). The second method is to subtract the
common/frequent wave from the rare/infrequent wave to obtain a ‘derived’
P300. The latter is used as part of a standard protocol in research done by
Tremblay (2002).
The mean latencies and amplitudes calculated separately for the P300 and
P300 Subtracted wave are depicted below in Figures 3.10 & 3.11.
42
University of Pretoria etd – Lombard, F D (2005)
Latencies: P300 and P300 Subtracted wave
350
314.7309.9
314.8313.4
314.6306.4
300
Latency (in ms)
250
200
Mean(P300)
150
Mean(P300 Subtracted)
Standerd Deviation (P300)
100
Standerd Deviation (P300 Subtracted)
50
0
40.3 34.6
34.2 34.5
37.2 34.6
Female
Male
Total
Mean(P300)
314.6
314.8
314.7
Mean(P300 Subtracted)
306.4
313.4
309.9
Standerd Deviation (P300)
34.2
40.3
37.2
Standerd Deviation (P300 Subtracted)
34.5
34.6
34.6
Figure 3.10: Comparison between latencies for the P300 and the P300
subtracted wave.
Amplitudes: P300 and P300 Subtracted wave
8
7
7.6
6.8
7.03
7.2
6.7
7.1
6.9
6.6
6.5
5.8
6
Amplitude (in uV)
6.7
6.4
5
4
Mean (P300)
Mean (P300 Subtracted)
3
Standard Deviation (P300)
2
Standard Deviation (P300 Subtracted))
1
0
Female
Male
Total
Mean (P300)
7.6
6.7
7.1
Mean (P300 Subtracted)
6.8
7.03
6.9
Standard Deviation (P300)
6.4
6.7
6.6
Standard Deviation (P300 Subtracted))
5.8
7.2
6.5
Figure 3.11: Comparison between amplitudes for the P300 and the P300
subtracted wave.
As indicated by these figures, the mean latency and amplitude values show
only marginal differences with female latencies consistently shorter and
43
University of Pretoria etd – Lombard, F D (2005)
amplitudes bigger than that of their male counterparts. No statistically
significant differences were found for any of these variables. Similarly, the
standard deviations for both the P300 and the P300 subtracted wave show
only marginal, insignificant differences. No significant effect for the marking
protocol/method was observed for the latencies and amplitudes of the P300
and P300 subtracted wave.
When examining the literature on the subject, it becomes clear that little or no
information has been published regarding the subject. Furthermore,
researchers tend not to disclose which method they have used when marking
the P300 responses.
In light of these findings it can be concluded that either method is valid. What
is essential is that the same method is used consistently throughout,
especially with the aim of creating a clinic-specific normative database, or to
be able to compare results to an existing clinic-specific database.
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University of Pretoria etd – Lombard, F D (2005)
4. Conclusion
The P300 response depends on attention to and discrimination of stimulus
differences. The main aim of this study was to determine the range of the
latency and amplitude values of the auditory P300 evoked response across
gender for a group of normal hearing young adults. This was achieved by
determining the average values of the latencies and amplitudes of these
waveforms and documenting the range of findings (mean, minimum,
maximum and standard deviations). These findings are summarised in Table
4.1.
Table 4.1: Summary of average findings and range of P300 and P300
subtracted wave.
Mean
Variable
P300
Latency
314.70
th
Median
th
75
Standard
25
Deviation
Percentile
37.20
287.28
311.7
342.17
6.6
2.28
4.54
9.69
34.60
286.7
305.45
331.33
6.5
2.6
4.85
9.41
Percentile
(in ms)
Amplitude 7.1
(in µV)
P300
subtracted
wave
Latency
309.90
(in ms)
Amplitude 6.9
(in µV)
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University of Pretoria etd – Lombard, F D (2005)
4.1. Critical evaluation of study
The implications of the clinical and research findings must be discussed in
comparison with the strengths and limitations of the present study, and the
P300 in general.
In the words of George von Békesy,” One of the most important features of
scientific research is the detection of errors. The writer believes that positive
results and failures ought to be discussed together.” (Von Békesy, 1960:7)
The present findings were consistent with a number of documented studies in
the literature and had one of the largest sample sizes (n=100). The
generalisation of the results of the present study was, however, limited by:
1. The age range of the research sample (18-30 years, mean age = 24)
2. The utilisation of only one specific test protocol.
In terms of sample size (n=100), a number of studies were found to use a
similar number of subjects. For instance Anderer et al. (1997), tested 58
subjects, Boutros et al. (1997), tested 40 and Picton et al. (1984) tested 72
subjects. Some of the other studies used even smaller sample sizes, varying
between 5 and 24 subjects (Theunissen, 2002; Nourse, 2000; Salamat &
McPherson, 1999; Wall et al., 1991; Polich et al., 1985; Michalewaski et al.,
1982). Thus, when comparing the current sample size to the literature, it
appears a statistically sound sample size to establish a clinic-specific
normative data base. Unlike the brainstem auditory evoked potentials, which
are very stable with well established normative parameters, the long latency
auditory evoked potentials are subject to variations from both extrinsic and
intrinsic factors. Due to these variations, establishing a normative database
requires precise specification of the stimuli, recording conditions, recording
environment, subject state (including age and various biological and
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University of Pretoria etd – Lombard, F D (2005)
psychological factors), and response tasks. According to McPherson (1996), a
sample size of 20 would be considered the absolute minimum to establish a
normative database, and a sample size of 50 subjects would prove to be a
statistically sound number for establishing a normative database.
Within this sample size, all the subjects were within the age range of 18-30
years. Although this limited age range implies that the findings can only be
compared to other findings from the same age group, it was essential to
establish this age limit, as age is generally accepted to have a significant
influence on the results of the P300. If a larger sample size (that includes
subjects from a greater age range) can be selected in future, a division of
subjects into different age groups could provide the researcher with agespecific normative data from many different age groups.
Concerning test protocol, the present study was conducted using only one
specific test protocol. The same protocol was used to evaluate all the
subjects, to rule out any influences that differences in protocol may have on
the results (e.g. Lew & Polich, 1993; Mertens & Polich, 1997). Limitations in
terms of time and equipment also influenced the decision to use a single
protocol. However, the exploration of different protocols will be of great value
in obtaining the most accurate and reliable results possible.
Owing to time and equipment constraints, the present study only recorded the
relevant potentials using pure tone stimuli. If the full clinical value of the P300
as a diagnostic tool is to be exploited, a protocol utilising speech stimuli must
be explored. In conventional audiometry, this will not only provide a means of
confirming the results obtained from the pure tone evaluation, but will also
provide an indication of the processing of speech information. Speech stimuli,
especially naturally produced speech tokens, can be used to measure the
neural detection of acoustic cues. In a study conducted by Tremblay et al.
(2003) it was found that auditory event-related potentials evoked by naturally
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University of Pretoria etd – Lombard, F D (2005)
produced speech sounds showed remarkable test/re-test reliability. Given this
stability, any significant alterations in morphology would likely reflect changes
in neural activation to speech, and not simply random variability. P300s
elicited using naturally produced speech sounds could be used to assess
changes in neural activity over time, after various types of rehabilitation such
as cochlear implants, hearing aid amplification, second language training and
auditory training (Tremblay et al., 2003; Tremblay & Krause, 2002). Obligatory
(N1) and discriminative (MMN, P3) cortical ERPs may provide useful indices
of improvement in audibility and discriminability of auditory stimuli provided by
hearing aids for the difficult-to-test patients with hearing loss, as well as
subsequent monitoring of the effectiveness of auditory training.
The present study only explored the recording of the P300 in the active or
attentive state, but can also be recorded using a passive or avoidance state
(Musiek & Lee 1999). In the avoidance situation, the P300 is either greatly
reduced or absent. A passive P300 requires no active counting of the rare
stimuli by the subject. On investigation of the literature available on P300
recordings, there is a great number of studies using the active or oddball
condition (e.g. Boutros et al., 1997; Anderer et al., 1996; Wall et al., 1991;
Jirsa & Clontz, 1990; Polich, Howard & Starr, 1985 Picton et al., 1984).
Studies recording the passive condition are less common. Some researchers
have found reduced P300 amplitudes in the passive condition (Pfefferbaum et
al., 1985), while others found no significant difference between P300 latency
and amplitude for the attentive (oddball) and passive tasks (Iwanami et al.,
1996).
Ford et al. (1997) investigated automatic and effortful processing in ageing
and dementia, using three different protocols for recording P300, of which one
was a passive condition. They found that regardless of the attention given to
the rare stimuli, the P300 was still smaller in elderly than in younger subjects.
They concluded that the performance task had no effect on the latency of the
P300. According to Hall and Mueller (1997), subject attention is important
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University of Pretoria etd – Lombard, F D (2005)
when measuring the conventional, attentive P300 responses, but not essential
when measuring the so-called earlier P3a response. These alternative options
for recording the P300 must be explored in future research, as a protocol that
requires less participation from the subject can be of great value in so-called
‘difficult-to-test’ populations.
‘Difficult-to-test’ populations are defined as patients who “cannot, for some or
other reason, participate sufficiently in conventional testing procedures”
(Schmulian, 2002:22). According to Hall (1992) these may be of any age
group, as most of the pathologies precluding voluntary participation are not
age related. Among these conditions are the following:
•
Intellectual limitations that will result in unreliable test results;
•
Emotional and psychological problems that may lead to inconsistent
responses and
•
Persons with suspected non-organic hearing loss.
A number of pathologies, of which patients can be classified as difficult-to-test,
have been evaluated using the P300. For instance, the P300 has been used
as a tool for the diagnosis of demeaning illnesses such as Alzheimer’s
disease (Fernandez et al., 2001). This particular condition may cause an
intellectual impairment that could lead to unreliable results when using a
protocol that requires wilful participation on the part of the subject.
A condition such as autism that has also been studied using the P300
(Ciesielki et al., 1990), may preclude voluntary participation due to the
emotional component of the condition. If the passive recording condition of the
P300 can be explored in order to establish a normative database for this
protocol, this may serve as a reference of normality, and will be greatly
beneficial when evaluating the populations that are unable to participate
wilfully in the evaluation.
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University of Pretoria etd – Lombard, F D (2005)
4.2. Recommendations for future research
The value of a clinic-specific normative database as suggested by Hall (2000)
has already been established. Recordings from clinical populations may be
compared to normative findings to determine whether the clinical findings fall
within the range of normality as defined by the normative data. The present
study’s findings compare favourably with a study by Theunissen (2002) at the
same clinic, utilising the same protocol. This study had a larger sample size
which can be used in combination with the study done by Theunissen (2002)
to establish the first clinic-specific normative database for the auditory P300
event-related potential at the University of Pretoria. Future research can utilise
this normative database to compare results and expand the database to
include more clinical populations. This will yield a larger, and therefore more
reliable, normative database.
Having established a normative database, the auditory P300 can now be
utilised for a variety of clinical purposes, including assessment of higher level
auditory processing. Event-related potentials (ERP), in combination with
behavioural measures, may be used to assess the higher level cognitive
processing involved in the discrimination and identification of complex stimuli
such as speech sounds. Electrophysiological and behavioural measures
provide insight into the timing, strength and location of early and later cortical
brain processes associated with auditory processing. Utilising these
measurements may provide insight into how sensori-neural hearing loss alters
the brain processes underlying auditory detection and discrimination (Oates,
Kurtzberg & Stapells, 2002).
The susceptibility of the late latency responses to the subject’s state of
consciousness might make it less useful in routine estimation of hearing
thresholds, but it is this very sensitivity to state of awareness that enables the
clinician to use these measurements in evaluating the higher auditory
functioning, such as auditory attention (Hall & Mueller, 1997) or recognition
50
University of Pretoria etd – Lombard, F D (2005)
and categorisation of sounds (McPherson, 1996). Its sensitivity to these
higher auditory functions makes it useful in the evaluation of disorders that
affect these skills, such as central auditory processing disorders (CAPD).
CAPD generally presents with normal peripheral hearing. Consequently the
traditional auditory tests for peripheral auditory function provide little or no
insight into CAPD. Studies conducted by Jirsa and Clontz (1990) and Jirsa
(1992) on the auditory P300 in children with Central Auditory Processing
Disorders (CAPD) have been of great importance to point out the clinical
value of these measures in providing some means of objective quantification
of the disorder. These researches found significant delays in the latencies of
the P300 potentials in children with CAPD.
Jirsa (1992) compared
behavioural changes resulting from intervention programs for CAPD, and
concluded that P300 latencies and amplitudes are sensitive to changes in
neural activity following an intervention program (Jirsa, 1992).
A further limitation of the use of P300s lies in the vast number of factors that
may influence these responses. These include factors such as gender, age
and medication that were controlled in the present study. Despite all the
controls that were put in place for this study, considerable inter-subject
variability still existed. This suggests that there are perhaps other unexplored
variables that could influence the P300 latencies and amplitudes. These
variables must be investigated in future research in order to determine their
effect on the P300 potentials.
A comprehensive test battery and cross-check principal remains the most
effect way to reduce the influences of variables and ensure a reliable and
valid diagnosis (Gravel, 1994). According to Hanley “the test battery is the
foundation of responsible and effective auditory assessment” (Hanley, 1986:
2).
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University of Pretoria etd – Lombard, F D (2005)
4.3. A final thought
Having discussed the general advantages and limitations of the P300, the
application of these measures in the current South African context must be
reviewed. It may be argued that the recording of these potentials requires
sophisticated equipment with large capital investment, which is not accessible
to a great percentage of the population. The current shortage of these
facilities must not force clinicians to be satisfied with less sophisticated
methods. Audiology is a rapidly expanding, and developing science and
audiology in South Africa can be no different. The clinical value of the auditory
P300 evoked potentials must continually be explored and examined, as it has
already been established that these potentials can be of great value in
assessment of a variety of pathologies. The electrophysiological assessment
of a disorder, such as CAPD may be of great value in a context where
linguistic and culturally sensitive methods for assessing these disorders are
not appropriate. Electrophysiological evaluation, such as auditory eventrelated potentials, is a low linguistically loaded assessment approach that is
not sensitive to linguistic and cultural diversity. In these cases an
understanding of the instructions for the performance task alone is required.
As scientists involved in the diagnosis and management of pathologies
affecting any part of the complete auditory system, local audiologists have the
responsibility to investigate any clinical tool that may be of value in delivering
a responsible and accountable service to the population of South Africa.
Epilogue: “And the end of all our exploring will be to arrive where we started
and know the place for the first time.” (T.S. Eliot, 1888-1965)
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University of Pretoria etd – Lombard, F D (2005)
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Appendix A: Consent Form
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APPENDIX B: Case History Form
Medical/Audiological History Questionnaire
Name: _____________________________________
D.O.B:_____________________________________
Date: _____________________________________
Occupation:________________________________
Gender: M
F
Subject identification no:
_____________________________________________________
_____________________________________________________
OTOSCOPY
Tick if no significant problem
Right:
Left:
AUDIOMETRY
Tick if no significant problem
Is there any marked asymmetry?
Description:
Other comment:
Significant air-bone gap?
Description:
Tick if there is a significant problem
EAR DISEASE
Otalgia
Discharge
Perforations
Ear Surgery
Left
Right
IN CONFIDENCE
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University of Pretoria etd – Lombard, F D (2005)
_____________________________________________________
HISTORY
Tick if there is a significant problem
Any previous hearing problems?
Left:
Right:
Description:
Description:
Tick if there is significant problem
HEARING
Onset:
Left
Right
Noise Exposure:
Ototoxic drugs:
Other:
Description:
Description:
BALANCE
Dizziness:
Description:
TINNITUS
Tinnitus:
Left:
Right:
CURRENT MEDICATION
Description:
Description:
Please specify any current medication:
OTHER MEDICAL HISTORY/PROBLEMS
Please tick if no significant problem
Psychiatric problems:
(Depression, schizophrenia)
Description:
Organic mental disorders:
Description:
(Epilepsy, dementia, head injury, stroke)
Alcoholism:
Description:
Please specify any other problems:
_____________________________________________________
IN CONFIDENCE
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University of Pretoria etd – Lombard, F D (2005)
Appendix C: Graphic illustration of ALLR
and AERP
Composite schematic of the components of the long latency auditory evoked
potentials and the event-related potentials (N100, P160, N200, CNV, Tcomplex, Processing negativity)
(From Late Potentials of the Auditory System, McPherson, 1996)
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University of Pretoria etd – Lombard, F D (2005)
Appendix D: Example of results
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University of Pretoria etd – Lombard, F D (2005)
Appendix E: Results (Raw data)
P300 amplitude raw data (µV)
Female
12.73
18.76
8
8.2
2.77
7.37
5.68
0.97
2.26
2.65
1.74
10.74
1.75
0.61
0.25
5.25
6.69
6.69
1.13
1.56
8.86
8.86
7.18
5.26
25.33
23.51
7.13
7.13
0.08
0.08
7.98
7.98
9.95
9.95
6.16
6.16
8.06
8.07
0.97
0.97
11.12
11.12
4.13
4.13
Male
2.69
3.25
7.75
5.27
6.2
8.04
0.48
2.31
22.49
13.98
13.64
12.26
5.75
8.66
9.68
8.85
2.29
0.18
3.94
0.41
2.43
2.24
13.49
9.73
20.11
6.11
1.24
0.69
37.59
10.16
9.94
2.88
2.88
1.75
1.75
5.14
5.14
2.52
2.52
12.79
12.79
2
2
6.82
Total
12.73
18.76
8
8.2
2.77
7.37
5.68
0.97
2.26
2.65
1.74
10.74
1.75
0.61
0.25
5.25
6.69
6.69
1.13
1.56
8.86
8.86
7.18
5.26
25.33
23.51
7.13
7.13
0.08
0.08
7.98
7.98
9.95
9.95
6.16
6.16
8.06
8.07
0.97
0.97
11.12
11.12
4.13
4.13
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University of Pretoria etd – Lombard, F D (2005)
4.29
4.29
15.31
15.31
22.68
22.68
6.82
1.66
1.66
3.74
3.74
3.74
4.29
4.29
15.31
15.31
22.68
22.68
2.69
3.25
7.75
5.27
6.2
8.04
0.48
2.31
22.49
13.98
13.64
12.26
5.75
8.66
9.68
8.85
2.29
0.18
3.94
0.41
2.43
2.24
13.49
9.73
20.11
6.11
1.24
0.69
37.59
10.16
9.94
2.88
2.88
1.75
1.75
5.14
5.14
2.52
2.52
12.79
12.79
2
2
6.82
6.82
1.66
1.66
3.74
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University of Pretoria etd – Lombard, F D (2005)
3.74
3.74
P300 subtracted wave amplitude raw data (µV)
P300 Sub Amp
Female
P300 Sub Amp
Male
8
8
8.96
8.96
3.31
3.31
6.21
1.75
5.1
3.16
2.23
11.28
3.3
1.77
1.36
5.18
5.22
5.22
0.26
0.59
6
10.31
4.26
0.26
21.02
19.21
9.56
9.56
0.01
0.01
5.84
5.84
12.94
12.94
0.63
0.63
2.6
2.6
2.72
2.72
12.41
12.41
4.76
2.08
4.69
1.32
4.27
3.39
6.04
3.64
1.96
23.83
10.97
18.22
4.94
8.66
8.66
11.36
11.36
0.52
4.18
3.56
3.76
1.73
1.99
13.06
9.97
16.26
3.06
3.84
1.48
41.24
21.3
7.47
10.34
4.34
4.34
2.21
2.21
7.14
7.14
7.14
7.14
7.83
7.83
2.14
P300 Sub Amp
Total
8
8
8.96
8.96
3.31
3.31
6.21
1.75
5.1
3.16
2.23
11.28
3.3
1.77
1.36
5.18
5.22
5.22
0.26
0.59
6
10.31
4.26
0.26
21.02
19.21
9.56
9.56
0.01
0.01
5.84
5.84
12.94
12.94
0.63
0.63
2.6
2.6
2.72
2.72
12.41
12.41
4.76
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University of Pretoria etd – Lombard, F D (2005)
4.76
4.43
4.43
20.61
20.61
15.4
15.4
2.14
6.17
6.17
0.65
0.65
3.74
3.74
4.76
4.43
4.43
20.61
20.61
15.4
15.4
2.08
4.69
1.32
4.27
3.39
6.04
3.64
1.96
23.83
10.97
18.22
4.94
8.66
8.66
11.36
11.36
0.52
4.18
3.56
3.76
1.73
1.99
13.06
9.97
16.26
3.06
3.84
1.48
41.24
21.3
7.47
10.34
4.34
4.34
2.21
2.21
7.14
7.14
7.14
7.14
7.83
7.83
2.14
2.14
6.17
6.17
0.65
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University of Pretoria etd – Lombard, F D (2005)
0.65
3.74
3.74
P300 Latencies raw data (ms)
Male
271.08
283.56
311.7
336.7
255.45
246.07
308.58
305.45
364.83
367.95
311.7
311.7
330.45
355.45
302.33
283.58
355.45
386.7
352.33
355.45
314.83
339.83
274.2
286.7
364.83
396.95
302.33
324.2
374.2
327.33
314.83
308.58
264.95
267.95
252.32
252.32
302.33
302.33
352.33
352.33
311.7
311.7
289.83
289.83
236.7
Female
330.45
346.08
336.7
346.08
274.2
267.95
324.2
314.83
349.2
339.83
267.95
292.95
333.58
330.45
305.45
227.32
283.58
283.58
274.2
271.08
333.58
333.58
346.08
352.33
358.58
392.95
305.45
305.45
302.33
302.33
336.7
336.7
333.58
333.58
299.2
299.2
299.2
299.2
336.7
336.7
264.83
264.83
302.33
302.33
380.45
Total
271.08
283.56
311.7
336.7
255.45
246.07
308.58
305.45
364.83
367.95
311.7
311.7
330.45
355.45
302.33
283.58
355.45
386.7
352.33
355.45
314.83
339.83
274.2
286.7
364.83
396.95
302.33
324.2
374.2
327.33
314.83
308.58
264.95
267.95
252.32
252.32
302.33
302.33
352.33
352.33
311.7
311.7
289.83
289.83
236.7
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University of Pretoria etd – Lombard, F D (2005)
236.7
342.95
342.95
352.33
352.33
380.45
274.2
274.2
321.08
321.08
236.7
342.95
342.95
352.33
352.33
330.45
346.08
336.7
346.08
274.2
267.95
324.2
314.83
349.2
339.83
267.95
292.95
333.58
330.45
305.45
227.32
283.58
283.58
274.2
271.08
333.58
333.58
346.08
352.33
358.58
392.95
305.45
305.45
302.33
302.33
336.7
336.7
333.58
333.58
299.2
299.2
299.2
299.2
336.7
336.7
264.83
264.83
302.33
302.33
380.45
380.45
274.2
274.2
321.08
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University of Pretoria etd – Lombard, F D (2005)
321.08
P300 subtracted wave latencies raw data (ms)
P300 Sub Lat
Female
336.7
336.7
346.08
346.08
274.2
274.2
324.2
374.83
364.83
321.08
267.95
289.83
330.45
383.58
305.45
230.45
286.7
286.7
277.33
271.08
261.7
271.08
264.83
280.45
355.45
396.08
305.45
305.45
299.2
299.2
336.7
336.7
330.58
330.58
299.2
299.2
299.2
299.2
308.58
308.58
267.95
267.95
302.33
302.33
296.08
274.2
P300 Sub Lat Male
274.2
305.45
299.2
336.7
255.45
246.07
296.08
305.45
371.08
336.7
311.7
314.83
302.33
302.33
283.58
283.58
386.7
355.45
355.45
308.58
314.83
299.2
274.2
289.83
367.95
392.95
302.33
324.2
389.83
330.45
302.33
308.58
333.58
333.58
252.32
252.32
302.33
302.33
302.33
302.33
308.58
286.7
286.7
321.08
321.08
355.45
P300 Sub Lat Total
336.7
336.7
346.08
346.08
274.2
274.2
324.2
374.83
364.83
321.08
267.95
289.83
330.45
383.58
305.45
230.45
286.7
286.7
277.33
271.08
261.7
271.08
264.83
280.45
355.45
396.08
305.45
305.45
299.2
299.2
336.7
336.7
330.58
330.58
299.2
299.2
299.2
299.2
308.58
308.58
267.95
267.95
302.33
302.33
296.08
274.2
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University of Pretoria etd – Lombard, F D (2005)
274.2
305.45
305.45
355.45
305.45
305.45
274.2
305.45
305.45
274.2
305.45
299.2
336.7
255.45
246.07
296.08
305.45
371.08
336.7
311.7
314.83
302.33
302.33
283.58
283.58
386.7
355.45
355.45
308.58
314.83
299.2
274.2
289.83
367.95
392.95
302.33
324.2
389.83
330.45
302.33
308.58
333.58
333.58
252.32
252.32
302.33
302.33
302.33
302.33
308.58
286.7
286.7
321.08
321.08
355.45
355.45
305.45
305.45
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University of Pretoria etd – Lombard, F D (2005)
Appendix F: Average latencies and
amplitudes for the ALLR (P1, N1 and P2)
Latencies: P1, N1 and P2
200
191.3 188.3
185.5
180
160
Latency (in ms)
140
123.7
120.1 121.9
120
100
94
89.9
85.8
Female
80
Male
Total
60
40
33.3
25.9 29.5
38.3
33.436.2
40.6
34.834.02
20
0
P1
N1
P2
Standerd Deviation Standerd Deviation Standerd Deviation
(P1)
(N1)
(P2)
94
120.1
191.3
33.3
33.4
Male
85.8
123.7
185.5
25.9
36.2
34.8
Total
89.9
121.9
188.3
29.5
38.3
34.02
Female
40.6
Average latency values for the P1, N1 and P2
Amplitudes: P1, N1 and P2
7.7
8
5.7
6
4.8
3.8
Amlitude (in uV)
4
3.2
3.8
3.5
2.6
2.4
2
1.6
0.6
2.5
1.3
1.1
Female
0.5
Male
0
Total
-2
-2.4
-3.5
-3
-4
Standerd Deviation Standerd Deviation Standerd Deviation
(P1)
(N1)
(P2)
P1
N1
P2
Female
2.6
-3.5
3.2
1.1
2.4
2.5
Male
0.6
-2.4
3.8
0.5
4.8
7.7
Total
1.6
-3
3.5
1.3
3.8
5.7
Average amplitude values for the P1, N1 and P2
84

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