1. SID 1027821
1
Thisdissertationissubmittedinpartfulfilmentof the BScHonours degree programme regulationsin
the Departmentof VisionandHearing,AngliaRuskinUniversity.
Word count 6000
Author: Nauris Veits
May 2015
EVALUATION OF CENTRAL AUDITORY
DEVELOPMENT USING CORTICAL AUDITORY
EVOKED POTENTIAL IN HEARING IMPAIRED
CHILDREN WITH COCHLEAR IMPLANTS
MOD 002497
2. SID 1027821
2
Acknowledgement
I would like to thank all Anglia Ruskin University staff who have been with us last nine
months. You have been fantastic!
Thanks to Phil, Eldre, Sri, Clare, Leah, Victoria and Fei.
I would like to thank my employer Jane Taylor for understanding and support.
Finally, I would like to thank my dear wife Anda for support.
I do apologise if I have forgotten someone and do greatly appreciate everyone's support
through my time at university!
3. SID 1027821
3
..We choose to go to the moon in this decade and do the other things, not because they are
easy, but because they are hard... JFK
4. SID 1027821
4
Abstract
Cortical auditory evoked potential (CAEP) wave P1 is a biomarker of maturity of the auditory
cortex. Delayed auditory stimulus in hearing impaired children presents longer and abnormal
P1 latency. Early intervention with cochlear implant(s), where hearing aids have failed, could
lead to successful maturation of auditory cortex.
Objective: Aim of major project is to review researches on Cortical Auditory Evoked
Potentials.
Aim 1: Age of implantation; early and late interventions affect on maturity of the
auditory cortex and P1 wave.
Aim 2: Factors that influence morphology of P1 wave.
Design: Reviewed four studies on CAEP published from 2002 to 2013.
Results: Children, fitted with CI up to age of 3 to 4 years demonstrate rapid change and shift
towards normal normative data in P1 latency over first 6 to 12 months after in-sound
experience. Reduction of amplitude of P1 wave is consistent as brain matures however, it has
broad variation across studies as different types of stimuli and test set-ups are used.
Conclusion: Resent studies consistently shows that P1 can be used as biomarker of maturity
of the auditory cortex and could be used as diagnostic tool in evaluation of efficiency of
cochlear implant(s) in children with hearing loss, particularly in difficult to test individuals.
However, further research in universal diagnostic test protocol would be required.
Key words: P1-N1-P2, plasticity of auditory cortex, children with hearing loss, cochlear
implants, morphology of P1 wave
5. SID 1027821
5
Table of contents
Introduction 1
P1-N1-P2 complex 6
Morphology of P1-N1 complex 6
Stimulus types 6
Delivery of stimuli 7
Analysis of studies 9
Literature review - methodology 9
Subjects 10
Stimulus presentations and recordings 10
Results 11
Discussion 20
Conclusion 24
References 25
6. SID 1027821
6
Introduction
Prevalence of congenital deafness in the UK is 1 in 1000 live births. Most common cause of
congenital deafness is syndrome, neo- or perinatal infection, trauma at birth, prematurity
and genetic predisposition. Incidence of hearing loss doubles in first 10 years of age.
Postnatal infections and health problems, time spent in intensive care (noise induced
hearing loss for not-well babies), syndromes, traumas and many other can be accounted for
cause of acquired hearing loss later on in life (NSC, 2006). Unaided hearing loss will delay
child's development of speech and language. In long term, it has broader impact on social
interaction, child's self-esteem, education and employability (Parfect, 2015). Since
introduction of newborn hearing screening in the UK in 2006, hearing impairment can be
detected few hours after birth and very young infants can be fitted with hearing aids as
early as few weeks old. Cochlear implants (CI) become beneficial in children with severe to
profound hearing loss where hearing aids have failed to provide efficient improvement.
Evaluation can be done with subjective and objective tests, additionally parents or carers
can monitor effectiveness of hearing aid or CI. Subjective testing, Visual Reinforcement
Audiometry provides information on benefit of the device. However, because it involves
conditioning and observing child, it does become more difficult and unreliable if child is not
cooperating or is not providing valid response. Although objectively, Auditory Brainstem
Response can measure performance of the hearing aid or CI, it will not provide access to
more detailed information on how the auditory cortex has responded to the sound and how
the sound is processed, and how it develops (Burkard, et.al. 2007).
Short latency potentials demonstrate function of cochlea or auditory nerve, and middle
latency demonstrates function of auditory. If short and mid latencies, require short stimulus
to elicit potential then Cortical Auditory Evoked Potential (CAEP) can be evoked either with
short stimulus or with longer, speech-like sounds (Burkard, et.al. 2007). In the last two
decades, CAEP has been used to evaluate impact of the cochlear implants on auditory cortex
as well as hearing aids and/or frequency transposition/compression. Late latency P1-N1-P2
complex can be used as a biomarker of maturity of the brain (Sharma, et.al. 2005; Dorman,
7. SID 1027821
7
et.al. 2007). In newborns, the latency of P1 is considerably greater, around 300ms, and in
adults it is much shorter - 60ms (Nash, et.al. 2007).
Some of the researches of the past decade have noted that use of the cochlear implants has
impact on latency of wave of P1. If hearing impaired infants and young children are left
unaided, maturation of P1-N1-P2 and later on negative,N2 wave, complex will be delayed.
Researches noticed if children get early cochlear implant, then 6-8 months after hook-up P1
latency shortens and is closer to the individual of same age and normal hearing (Sharma,
et.al. 2002; Nash, et.al. 2007; Jiwani, et.al. 2013; Alvarenga, et.al 2013).
As a diagnostic tool evaluation of CAEP can be used to investigate disorders affecting central
processing of sound, estimate threshold sensitivity, monitor changes in hearing system with
the hearing loss and evaluate outcome of rehabilitation of hearing aids and CI (Burkard,
et.al. 2007; Glista, et.al. 2012).
Figure 1 (reprinted from
Burkard, et.al. 2007)
Auditory Evoked Potentials
in relation of the auditory
pathway.
8. SID 1027821
8
Evidence from animal experiments proposes that sound deprivation affects dendritic
development (McMullen and Glaser, 1988). The P1-N1-P2 complex in infants starts with P1
wave at 200-250 msec after onset of stimulus. Up to age of ten, N1 wave is not very
prominent. Over the years, P1 latency becomes shorter until it stabilises; N1 and P2 waves
emerge. It is suggested, that sound deprivation in early childhood leads to subnormal
myelination (Moore and Linthicum, 2007). Hypomyleination affects velocity of conduction
therefore prolonged P1 can be observed (Sharma, et.al., 2002). Later in life, N1 and P2
latencies show changes in aging adults (Burkard, et.al., 2007).
Figure 2 (reprinted from ASHA,n.d.) Short,middleand late latenciesand averagewavepeak times.
9. SID 1027821
9
P1 latency in normal hearing individuals (average values):
Infants = 300ms
3 years = 125ms
15 years = 95ms
Middle-aged = 60ms (Nash, et.al., 2007)
Ponton and Eggermont (2001) suggest the P1 matures at age of 12 and changes very little
after that. In congenitally deaf children development of P1 latency is delayed and auditory
brain is vulnerable to be taken over by non-auditory networks, e.g. by visual cortex (Moore
and Shannon, 2009). Negative wave, N1 latency's, absence in CI users who have been deaf
for period of 3 years below of age of 6 could have potentially poor performance in
perception of degraded speech later in life (Eggermont and Ponton, 2003).
Figure 3 (reprinted from Sharma, et.al, 2001) P1 latencies in normal hearing individuals.
Shortening of latency as auditory cortex matures.
10. SID 1027821
10
The aim and outline of the dissertation
For the major project, literature review was conducted. In total four researches by Sharma,
et.al. 2002; Sharma, et.al. 2005; Hossain, et.al. 2013; and Alvarenga, et.al. 2013 were chosen
and reviewed.
The key words used for search: cortical auditory evoked potential; cochlear implant; hearing
impaired children; maturity of the brain; plasticity; P1 latency; P1-N1-P2; late latency.
Databases used: sciencedirect.com (Elsevier); journals.lww.com (LWW); ncbi.nlm.nih.gov
(PubMed); ovidsp.ovid.com (Ovid). Access, for some publications, via Anglia Library was
used. Databases gave access to e-journal publications, e.g. Ear and Hearing; American
Academy of Audiology; International Journal of Audiology.
Although CAEP has been known for decades, only in recent years it has been researched in
more details. There is very little data on hearing aid amplification and congenital hearing
loss, and CAEP. Therefore, cochlear implants in children, congenital hearing loss and CAEP
were chosen as it provided sufficient and reliable data for literature review.
Main interest is how the age of subject and length of auditory deprivation when CI is
implanted affects maturity of the auditory cortex, especially P1 latency from P1-N1-N2
complex.
Studies use various types of stimulus: speech like sounds or tone bursts. Therefore,
additional interest is in morphology, latency and amplitude, of the P1 wave and how it
changes depending on various types of stimulus used. Hopefully, there could be drawn
conclusion on what test set-up are most reliable for repeatability of P1 latency recordings
and could be used in further studies about CAEP.
Chapter 2 describes in more details morphology of P1-N1-P2 latency complex and different
types of stimulus that can be used to elicit P1 wave. Chapter 3 analyses four studies;
subjects, procedures and their results. Discussion summarise finding on plasticity of auditory
cortex and advantages/disadvantages of different types of stimulus. Finally, conclusion
draws summary on findings and proposes future study.
11. SID 1027821
11
P1-N1-P2
Morphology of P1-N1 complex
Cortical Auditory Evoked Potentials (CAEP) can be recorded from very early age. Firstly, late
evoked potential changes as brain matures demonstrating plasticity of young auditory
cortex; other changes of latency depends on hearing threshold, and integrity of auditory
cortex, e.g. auditory processing disorders. Secondly, morphology of P1-N1-P2 latency
complex depends to characteristics of stimulus (Brown, et.al. 2008).
P1-N1-P2 complex late cortical responses are obligatory responses that depend on the
physical properties of the stimulus, its intensity and frequency (Purdy, et.al. 2002). Adults
have small P1 amplitude <2 µV, however, in children P1 amplitude is larger (Sharma, et.al.
1997). In opposite, N1 negative peak in adults has large amplitude average 2-5 µV,
depending on stimulus parameters. Children can be absent N1 negative wave if N1
generator in auditory cortex is immature and/or if stimulus is presented rapidly. N1 negative
wave starts to emerge later on in life (Ceponiene, et.al. 2002). Therefore, lack of N1 wave
will contribute to longer P1 latency. Deprivation of auditory cortex delays development of
N1 wave and respectively P1 will have longer latency compared to children with normal
hearing and same age group (Ponton and Eggermont, 2001).
Amplitude of P1-N1-P2 increase with stimulus intensity although may saturate at intensities
exceeding 60 - 80 dB normal hearing level (Burkard, et.al. 2007; Purdy, et.al. 2012).
Increased stimulus frequency reduces amplitude of P1-N1-P2 complex and opposite, if
frequency of stimulus decreases then latencies increase (Burkard, et.al. 2007).
Stimulus types
CAEP can be elicited with shorter tone burst or longer speech like stimulus (Brown, et.al.
2008). Cone and Whitaker (2014) used four tone bursts: 50ms tokens at 0.5, 1.0, 2.0 and 4.0
12. SID 1027821
12
kHz; and 7 speech tokens (50ms long): /a/, /i/, /o/, /u/, /m/, /s/, and /∫/; Hossain, et.al.
(2013) /m/, /g/, and /t/ synthesized speech; Sharma, et.al. (2002 and 2005) used
synthesised syllable /ba/ (90ms long); Alvarenga, et.al. (2013) pre-recorded live voice /da/
(180ms long); Jiwani, et.al. (2013) 500Hz tone bursts (36ms long).
Burkard, et.al. (2007) writes that it is possible to obtain P1 latency by using variety of
stimuli. Speech like sounds are more complex and can interact among various acoustic
parameters. Therefore, result could be affected comparing to simple stimuli. Natural speech
sounds gives access to evaluation on processing speech in cortical level.
Studies have noticed that complex syllable interact between vowel and consonant sounds. It
affects cortical potential, normally reducing amplitude of wave. Complex sounds, in P1-N1-
P2 recordings, can overlap in auditory cortex therefore demonstrating less response. It
demonstrates that auditory cortex has areas overlaying each other. Ostroff, et.al. (1998)
researched CAEP response from /sei/ syllable. Response of CAEP from more complex /sei/
stimulus is smaller comparing if stimulus is separated in /s/ and/ei/ where /ei/ produced
potential with greater amplitude.
Syllables stimulus can be extracted and transformed from pre-recorded live voice or
generated synthetically. Swink and Stuart (2012) researched tone and speech as stimuli
affect on P1-N1-P2 parameters. They used 723Hz tone burst, naturally and synthetic,
produced /a/ tokens. Latencies were shorter when evoked with tonal stimulus compared to
speech stimulus. Natural speech had shorter latencies compared to synthetic speech. It is
due to duration of stimulus: tone burst was 70ms and speech token 400ms. Natural and
synthetic speech tokens have no significant difference in amplitude, however it was smaller
for tonal stimulus.
Delivery of stimuli
Very little studies and guidance are on how the stimulus delivery has to be set up.
Therefore, it has been left up to the research teams' interpretation how to choose type of
delivery of stimulus. P1-N1-P2 complex recordings are more flexible in respect of stimulus
13. SID 1027821
13
selection, presentation and recordings. Most importantly, all test parameters have to be the
same across the test subject (Burkard, et.al. 2007).
Stimulus can be presented via loudspeaker or directly to the cochlear implant. Hossain,
et.al. (2013) had loudspeaker placed at 0' angle, Sharma, et.al. (2002 and 2005) had it 45',
and Alvarenga, et.al. (2013) at 90'. Jiwani, et.al. (2013) used earphone for stimulus
presentation. Study by Glista, et.al. (2012) delivered signal directly via audio shoe
minimising effects of room acoustics. Despite the variation of test set-up, all of above
mentioned studies had produced valid result.
14. SID 1027821
14
Analysis of studies
Literature review - methodology
Four researches were chosen for literature review. Online databases to search for
publications were used. Mostly used:
sciencedirect.com (Elsevier)
journals.lww.com (LWW)
ncbi.nlm.nih.gov (PubMed)
ovidsp.ovid.com (Ovid)
Databases gave access to e-journal publications, e.g., Ear and Hearing; American Academy
of Audiology; International Journal of Audiology, which are reputable, international journals.
PubMed had free access to some articles, however, for other literature, access via Anglia
Library website was used. For background reading on theory of subject books from Anglia
Library were borrowed.
Database search criteria:
Articles and publications with full access only
Language of publication - English as translating from other languages was not viable
Key words used for searching appropriate literature: cortical auditory evoked
potential; cochlear implant; hearing impaired children; maturity of the brain;
plasticity; P1 latency; P1-N1-P2; late latency; morphology of P1; latency and
amplitude of P1 .
Although CAEP has been known since mid 1930's, cochlear implants and maturity of the
auditory cortex is subject researched in last two decades, therefore it was not needed to
narrow down when studies were conducted.
In total four main researches by Sharma, et.al. 2002; Sharma, et.al. 2005; Hossain, et.al.
2013; Alvarenga, et.al., 2013 were chosen and reviewed.
15. SID 1027821
15
Subjects
Number of individuals they had studied - from 2 to 104. Age of subjects from 0-18 years.
Most of them had pre-lingual deafness and received single cochlear implant either shortly
after diagnosing hearing impairment or later on in life.
Sharma, et.al. (2002) had 121 hearing impaired children aged 2.3 to 18 years fitted
with cochlear implants. Additionally, 51 normal hearing children aged 0.1-20 years
were tested and used as a control group.
Sharma, et.al. (2005) study had 3 hearing impaired subjects. Two had hearing aids
prior CI and one of children was fitted with the hearing aids only. Age of subjects
with CI 15 and 25 months.
Alvarenga, et.al. (2013) recorded CAEP from ten children fitted with CI. Age of
subjects at the time of test was 1-5 years. Cortical auditory evoked potential was
recorded at activation of CI, after three and six months. Study did not have control
group of normal hearing children, therefore, results were compared to normative
data from literature.
Hossain, et.al. (2013) study recorded CAEP responses of 30 pre-lingual hearing
impaired children aged 0-15 years. Group 1 had 21 subjects with mean age of 3.2
years and sound depravation average 1.5 years; Group 2 had 9 subjects and mean
age of 10.4 years and sound deprivation of 8.3 years. P1 latency was recorded at 6
and 12 months post operative. Results of study were compared to normative values
from literature.
Stimulus presentation and recording
Sharma, et.al. (2002) study recorded CAEP by presenting synthetic speech syllable
/ba/. Duration of syllable - 90ms. Stimulus was presented via loudspeaker at an angle
of 45'. Eye movements monitored during recording. CAEP recorder 6 months after
implantation of CI.
As previously in study from 2002, Sharma, et.al. (2005) used the same protocol and
recorded CAEP by playing syllable /ba/. P1 of Subject 1 was recorded at 1 and 3
16. SID 1027821
16
Figure 4 (data collected from
Alvarenga, et.al. 2013) Reduction in
latencies for test group at average
age of 2y 5m. Compared to average
normal latency. Measured from
hook-up of CI to 6 months post
implantation.
months post hearing aids and at hook-up of CI, 3 and 12 months post operative.
Subject 2 had P1 recorded at 10 months post hearing aid and 1, 6, and 18 months
post CI fitting.
Alvarenga, et.al. (2013) presented /da/ stimulus; duration of one stimulus token -180
ms (extracted from live voice recording). Presented via loudspeaker positioned at
90'. Eye movements monitored.
Hossain, et.al. (2013) used stimulus /m/, /g/, and /t/ (synthesised speech syllable)
presented via loudspeaker and positioned at 0'.
(Table 2 Summary of test subjects and procedures from each study)
Results
Alvarenga, et.al., (2013) study concludes that P1 latency shortens as time of cochlear
implant use increase and reach normal normative value at age of 2.5-3 years.
For subject of mean age 2y 5m normal hearing latency is in range of 100-135 ms.
313.8
259.7
177.8
115
0
50
100
150
200
250
300
350
Mean latency (ms)/ avg.
age 2y5m
Activation
3 months
6 months
Normal
latency for
2y5m
17. SID 1027821
17
Mean Median Min Max
Age at activation 2y 5m 2y 4m 1y 2m 4y 3m
Latency (ms) at activation 313.8 305.50 290.00 365.00
Latency at 3 months 259.70 280.00 163.00 311.00
Latency at 6 months 177.80 150.00 99.00 275.00
Amplitude (µs) at activation 4.85 4.72 1.58 8.77
Amplitude at 3 months 2.46 2.38 1.12 5.13
Amplitude at 6 months 3.05 3.30 1.27 4.92
Table 2 (data from Alvarenga, et.al. 2013) Summary of P1 latencies and amplitudes
290
163
99
305.5
280
150
365
311
275
0
50
100
150
200
250
300
350
400
Activation 3 m 6 m
Min 1y 2m
Med 2y 4m
Max 4y 3m
Figure 5 (data collected from Alvarenga, et.al. 2013), Age of subject and time in auditory depravation in
relation to reduction of P1 latency.Early, successful,intervention shortens P1 latency. For early implanted
children P1 sooner reaches normal value.
18. SID 1027821
18
Figure 6 (left; data collected from
Alvarenga, et.al. 2013) Average change of
amplitude across all test subjects. First, it
shows reduction of amplitude after 6
months of CI hook-up, but then amplitude
increases slightly.
Figure 7 (bottom; data collected from
Alvarenga,et.al.2013) Changeof amplitude
after switch-on of the CI. Early and middle
implanted group hasreduction of amplitude
after 3 months however has slight increase
of amplitudeafter6 months.Late implanted
group hassteadily reduction of amplitude of
P1 after 3 and 6 months.
4.85 µs
2.46 µs
3.05 µs
0
1
2
3
4
5
6
Mean amplitude (µs)
2y5m
Activation
3 m
6 m
1.58 µs
1.12 µs 1.27 µs
4.72 µs
2.38 µs
3.32 µs
8.77 µs
5.13 µs
4.92 µs
0
1
2
3
4
5
6
7
8
9
10
Activation 3 m 6 m
Min 1y2m
Med 2y 4m
Max 4y3m
19. SID 1027821
19
Figure 4 and 5 demonstrate shortening of P1 latency from 313.8 ms at the moment of
activation of CI to 177.80 ms after 6 months of in-sound experience. Early implanted
children demonstrate reduction of P1 latency from 290 to 99 ms. For late implanted
children with average of 4y 3m latency reduced from 365 to 275 ms.
P1 amplitude reduces after 3 months of activation in early and middle group, however,
there is slight increase after 6 months. Late implanted group demonstrate greater amplitude
and has gradual reduction of P1 amplitude from hook-up of CI to 6 months post
implantation (Figure 6 and 7).
Hossain, et.al. (2013) study finds that children with hearing loss up to 3 years reach normal
value of P1 latency in 6 months after CI hook-up. However, children with 6 years of sound
deprivation do not reach normal value of P1 even after 12 months of CI use (Figure 8).
Group 1 (early implanted children) - P1 latency was 156 msec 6 months post-implant and
119.7 msec 12 months post-op. Change in amplitude was from 7.17 µsec (6 months post-
implant) to 9.49 µsec 12 months post implant.
Group 2 (late implanted children) - P1 latency had changed from 267.7ms to 232.6ms 6 and
12 months after implantation. Amplitude had changed from 3.75 µsec to 5.78 µsec 6 and 12
months after implantation.
20. SID 1027821
20
156.2
267.7
119.7
232.6
110
70
0
50
100
150
200
250
300
Group 1/ mean age 3.2 years Group 2/ mean age 10.4 years
6 months post-implant
12 months pots-implant
Average latency for normal hearing
subject
7.17
3.75
9.49
5.78
0
1
2
3
4
5
6
7
8
9
10
Group 1/ mean age 3.2 years Group 2/ mean age 10.4
6 months post-implant
12 months post implant
Figure 8 (data collected from Hossain, et.al 2013) P1 latency reduction after 6 and 12 months after
CI switch-on
Figure 9 (data collected from Hossain, et.al 2013) Change of P1 amplitude in early and late implanted
subjects
21. SID 1027821
21
Although, study by Sharma, et.al. (2005) does have 2 CI subjects only and does not have
control group, it is worth to review it more detailed because results very well demonstrate
plasticity of the brain. P1 latency becomes shorter in following months after fitting of the
cochlear implant and reaches normal value in average 6 months.
Subject 1 (Figure 10) did not show improvement from hearing aid therefore was fitted with
CI at age of 25 months. Reduction of P1 latency was from 200ms at hook up of CI to 120ms
after 12 months with CI, which correspond to latency of normal hearing child.
Figure 10 (reprinted from Sharma, et.al 2005) Subject 1
22. SID 1027821
22
Subject 2 (Figure 11) failed to gain benefit from hearing aid and had CI fitted at age of 10
months. Latency of P1 wave after 1 month with CI was 280ms and shortened to 130ms after
18 months in-sound experience.
Although no data on amplitude change of P1 wave have not been given, examining
morphology of CAEP wave can notice reduction of amplitude of P1 wave as auditory cortex
matures by having access to the auditory stimulation.
Age at activation 25 months 10 months
Latency (ms) at activation 200
Latency after 1 month 280
Latency after 6 months 130 200
Latency after 12 months 120
Latency after 18 months 130
Table 3 (data collected from Sharma, et.al. 2005). Average latencies from Subject 1 and 2
Figure 11 (reprinted from Sharma, et.al 2005) Subject 2
23. SID 1027821
23
Sharma, et.al. (2002) conducted study with more participants, involving 104 hearing
impaired children and 136 subjects with normal hearing in control group. Their study finds
that the optimal age for CI is up to 3.5 years as at that age the auditory cortex is the most
plastic.
Group of early implanted (average age of 3.8 years) and CI experience under 3.5 years
shows shortening of P1 latency after 6 months of switch on of the CI and has normal value
of P1 latency if compared to normal hearing children of same age (Figure 12).
Late implanted children of average age of 15.1 years and CI experience up to 3.1 years
demonstrate delay in maturation of P1 latency. Development of P1 latency is delayed by
100 ms even after prolonged exposure to the sound (Figure 13).
No data of P1 amplitude was given, and was not investigated or analysed.
Figure 12 (reprinted from Sharma, et.al. 2002)
P1 latency in normal hearing subjects (top
response) compared to early implanted group
(bottom response) after 6 months with CI
experience.
Figure 13 (reprinted from Sharma, et.al.
2002) P1 latency in normal hearing
subjects (top response) compared to late
implanted group (bottom response) after
6 months with CI experience.
24. 20
Table 2 (Summary of test subjects and recording methodology)
Number of
hearing
impaired
subjects
Number of
control
subjects with
normal
hearing
Age of hearing impaired
subjects
Stimulus (type and presentation) Other
Sharma, et.al.
2002 104 136
Age 1.3-17.5 yrs + 3 congenitally
deaf adults (18; 21 and 34)
Synthesised /ba/ stimulus; 90msec;
via loudspeaker at 45'
Eye movement monitor;
6 months after CI switch
on
Sharma, et.al.
2005 2
compared to
normative
data from
literature
15 and 25 months old Synthesised /ba/ stimulus; 90msec;
via loudspeaker at 45'
Eye blinking monitor
Hossain, et.al.
2013
30
compared to
normative
data from
literature
Group 1: 0-8 years
Group 2: 8-15years
Synthesised /m/, /g/, and /t/; via
loudspeaker at 0'
Two recordings: 6 and 12
months post
implantation
Alvarenga,
et.al. 2013
10
compared to
normative
data from
literature
1-5yrs Live voice token, pre-recorded /da/
stimulus; 180 msec duration; free
field at 90'
Recordings at CI
activation; 3 months and
6 months after
implantation; Eye
movements monitored
25. 20
Discussion
Plasticity of auditory cortex
Four studies examined maturity and plasticity of auditory cortex in hearing impaired
children with cochlear implants. Age of patients varies from few months old infants to
young adults aged 18. Most of them had pre-lingual deafness or had very little exposure to
speech and did not have speech processing disorders. Cochlear implant experience varied
from few months to several years. All of four studies conclude that early intervention with
cochlear implant proves to help with maturation of the auditory cortex. In average, age up
to 3-4 years is the threshold for successful outcome. P1 wave from P1-N1-P2 latency
complex is a biomarker of plasticity and maturation of the auditory cortex (Sharma,et.al.
2005; Dorman, et.al. 2007). Latency, for under 3 year old, with hearing impairment prior
hook up of cochlear implant was 100 -200 msec longer if compared to normal hearing child
at same age group (Sharma, et.al. 2005; Alvarenga, et.al. 2013). Once the implant was
activated, P1 latency went through sudden transformation and in following 6 to 12 months
reached normal hearing child's value. Auditory cortex is highly plastic at early age and
responds well to stimulation even after some time sound deprivation. Early intervention
helps to stop reorganisation of auditory pathway although some studies suggest that
permanent reorganisation of central auditory system has occurred (Gilley, et.al. 2008).
Children who had cochlear implants fitted after age of 3 - 4 years shows longer, more
delayed P1 latency, and normally they do not reach normal values. Jiwani, et.al. (2013)
research notes that even after 16 years in-sound experience, P1 latency is still more delayed
than normal hearing individual does. Sharma, et.al. (2002) and Alvarenga, et.al. (2013)
studies demonstrate delayed P1 latency by 50 - 100 msec even after prolonged use of the
cochlear implant. It confirms that at early age auditory cortex is vulnerable to lack of
auditory input, however is flexible enough to develop cortical pathways if receives early
intervention (Moore and Linthicum, 2007; Gilley, et.al. 2008).
26. SID 1027821
26
To demonstrate efficiency of early intervention with CI, Sharma, et.al. (2002) had 3 adult
patients aged 20, 33 and 35 who were congenitally deaf and their average use of cochlear
implant was 3.2 years. At the time of assessment, their P1 latencies were in average 50
msec longer compared to adults at same age and normal hearing.
If auditory stimulation is delayed, then some pathways can be taken over by visual cortex. In
late implanted subjects, studies demonstrate activation of visual pathways in response to
auditory stimulus (Gilley, et.al. 2008; Moore and Shannon, 2009).
Late fitting of CI will result in underdeveloped auditory cortex, which can demonstrate poor
speech perception. Morphology of P1 wave will be same as in subjects with normal and fair
speech discrimination, however, subjects with fair speech perception will have larger than
normal amplitude of negative N1 wave (Gordon, et.al. 2008). In contrast, Alvarenga, et.al.
Figure 14 (reprinted from Sharma, et.al. 2007) demonstrate CI implant influence to P1 latency
depending on ageof subject,length of sound deprivation and time in-sound exposure. In young
subjects up to age of 3.5-4 years auditory cortex goes through rapid development once CI is
activated.
27. SID 1027821
27
(2013) study additionally found no correlation between speech perception performance and
P1 development, and morphology of wave.
Stimulus influence to morphology of P1 wave
P1-N1-P2 latency complex goes through extraordinary transformation as the auditory cortex
develops. P1 wave becomes shorter and amplitude reduces; N1 negative wave can be
absent in young, undeveloped auditory cortex and gradually appear after age of 3 (Burkard,
2007; Hall, 2007).
Study by Alvarenga, et.al. (2013) finds reduction in amplitude of P1 just after 3 months of CI
use. Slight increase in amplitude appears at second measurement after 6 months of CI hook-
up. Interestingly, they found increased amplitude of P1 wave comparing between early
implanted group at age of 1year 2months (1.58 µs at CI activation) and late implanted group
of age 4years 3months (8.77µs at CI activation). Hossain, et.al. (2013) firstly, demonstrate
overall reduction of amplitude with age which correspond with previous studies, and,
secondly, increased amplitude of P1 wave after 12 months of hook-up of CI in early and late
implanted groups. Auditory cortex habituation to CI results to increased amplitude and
better morphology of P1 wave after activation of CI. Study by Sharma, et.al. (2005) does not
provide details on values of P1 amplitude, nevertheless visual inspection of P1 amplitude
demonstrate reduction of amplitude with experience if CI. All studies agree and confirm
reduction of P1 latency as cortex receives auditory stimulation and matures. However,
results on amplitude of P1 have more variations. Results from both studies by Alvarenga and
Hossain contradict with general perception on reduction of P1 amplitude as auditory cortex
develops (James, 2007). One of the reasons for such variations could be different type of
stimulus used and different set up of delivery.
Although data from literature reviewed has variations in amplitude values and tends to be
contradictory it corresponds with general conclusion that amplitude of P1 wave depends on
stimulus, its frequency and intensity. Alvarenga, et.al. (2013) used /da/ syllable natural pre-
recorded extraction from live voice where second study by Hossain, et.al. (2013) used
28. SID 1027821
28
shorter and synthesised stimulus /m/, /g/, and /t/. Simpler stimulus will elicit greater
amplitude compared more complex syllable (Ostroff, et.al, 1998).
29. SID 1027821
29
Conclusion
Auditory cortex is most plastic up to age of 3-4 years, therefore, early intervention with
cochlear implants proves to demonstrate the most benefit. P1 latency can be used as
biomarker to track development of auditory cortex and can be used as a diagnostic tool in
evaluation of efficiency of cochlear implant in children with hearing loss. For early implanted
children of age of 3-4 years, P1 latency goes through rapid transformation in first 3-6
months from activation of cochlear implant. It demonstrates plasticity of auditory cortex in
infants and returns to normal state soon after stimulation of sound. For later implanted
children it takes much longer for P1 latency to shorten and even after prolonged use of
cochlear implant, it often it does not reach normal normative value. It confirms that most of
the auditory pathway reorganises and develops up to age of 3-4 years. Additionally,
underdeveloped auditory cortex can result in poorer speech discrimination.
Morphology of P1 wave depends on test stimulus. It can be elicited by simple, short tone
bursts or by more complex, longer speech sounds, e.g., /m/, /t/, /da/, /ba/ etc. Test set-ups
and tones can be interpreted differently therefore, morphology of P1 wave varies across
studies. To achieve valid test results of P1 latency measurement, is to use exactly same
parameters for all subjects.
It does arouse a question on test protocol for diagnostic testing. Measurement of CAEP P1-
N1-P2 wave complex is a valid tool in evaluating fit if cochlear implant. It is particularly
valuable for difficult to test patients where subjective response can not be obtained. Further
studies would be required to create protocol for diagnostic testing purposes. It would
require a simple tone burst as stimulus (easier to replicate) and further research on delivery
of stimulus, e.g. positioning of speaker, and speaker vs. ear-inserts and audio-shoe.
30. SID 1027821
30
References
Alvarenga, K. de F., Vicente, L.C., Lopes, R.C.F., Ventura, L.M.P., Bevilacqua, M.C. and Moret,
A.L.M., 2013. Development of P1 cortical auditory evoked potential in children presented
with sensorineural hearing loss following cochlear implantation: a longitudinal study. CoDAS
[e-journal] 25(6) Available through: PubMed < http://www.ncbi.nlm.nih.gov/> [Accessed 4
April 2015]
ASHA, n.d. Picture of short, middle and late latencies [jpg] Available at:
<http://www.asha.org/uploadedImages/RP1987-00024_335_f29.gif> [Accessed 10 April
2015]
Brown, C.J., Etler, C., He, S., O’Brien, S., Erenberg, S., Kim, J.R., Dhuldhoya, A.N. and Abbas,
P.J, 2008. The Electrically Evoked Auditory Change Complex: Preliminary Results from
Nucleus Cochlear Implant Users. Ear and Hearing [e-journal] 29(5) Available through:
PubMed < http://www.ncbi.nlm.nih.gov/> [Accessed 10 April 2015]
Burkard, R.F., Eggermont, J.J., and Don, M., 2007. Auditory evoked potentials: basic
principles and clinical application. London : Lippincott Williams & Wilkins
Ceponiene, R., Rinne, T. and Näätänen, R., 2002. Maturation of cortical sound processing as
indexed by event-related potentials. Clinical Neurophysiology [e-journal] 113(6) Available
through: PubMed < http://www.ncbi.nlm.nih.gov/> [Accessed 10 April 2015]
Cone, B. and Whitaker, R., 2013. Dynamics of Infant Cortical Auditory Evoked Potentials
(CAEPs) for Tone and Speech Tokens. International Journal of Pediatriatic
Otorhinolaryngology [e-journal] 77(7) Available through: PubMed <
http://www.ncbi.nlm.nih.gov/> [Accessed 11 April 2015]
Dorman, M.F., Sharma, A., Gilley, P., Martin, K. and Roland, P., 2007. Central auditory
development: Evidence from CAEP measurements in children fit with cochlear implants.
Journal of Communication Disorders [e-journal] (40) Available through: ScienceDirect
<http://www.sciencedirect.com> [Accessed 12 February 2015]
Eggermont, J.J. and Ponton, C.W., 2003. Auditory-evoked Potential Studies of Cortical
Maturation in Normal Hearing and Implanted Children: Correlations with Changes in
31. SID 1027821
31
Structure and Speech Perception. Acta Otolaryngology [e-journal] 123 Available through:
EBSCOhost < https://www.ebscohost.com/> [Accessed 8 April 2015]
Gilley, P.M., Sharma, A. and Dorman, M.F., 2008. Cortical reorganization in children with
cochlear implants. Brain Research [e-journal] 1239 Available through: ScienceDirect
<http://www.sciencedirect.com> [Accessed 26 April 2015]
Glista, D., Easwar,V., Purcell, D.W. and Scollie, S., 2012. A Pilot Study on Cortical Auditory
Evoked Potentials in Children: Aided CAEPs Reflect Improved High-Frequency Audibility with
Frequency Compression Hearing Aid Technology. International Journal of Otolaryngology [e-
journal] 2012 Available through: Hindawi < hindawi.com> [Accessed 3 January 2015]
Gordon, K.A., Tanaka, S., Wong, D.D.E. and Papsin, B.C., 2008. Characterizing responses from
auditory cortex in young people with several years of cochlear implant experience. Clinical
Neurophysiology [e-journal] 119 Available through: ScienceDirect
<http://www.sciencedirect.com> [Accessed 25 April 2015]
Hall, J.W, 2007. New handbook of auditory evoked responses. Pearson Education Inc: Boston
Hossain, M.D., Raghunandhan, S., Kameswaran, M. and Ranjith, R., 2013. A Clinical Study of
Cortical Auditory Evoked Potentials in Cochlear Implantees. Indina Journal of Otoryngology
Head Neck Surgery [e-journal] 65(3) Available through: PubMed <
http://www.ncbi.nlm.nih.gov/> [Accessed 10 April 2015]
Jiwani, S., Papsin, B.C. and Gordon, K.A., 2013. Central auditory development after long-
term cochlear implant use. . Clinical Neurophysiology [e-journal] 124 Available through:
ScienceDirect <http://www.sciencedirect.com> [Accessed 12 February 2015]
McMullen, N.T. and Glaser, E.M., 1988. Auditory cortical responses to neonatal
deafening: pyramidal neuron spine loss without changes in growth or orientation.
Experimental brain research [e-journal] 72 (1) Abstract only. Available through :<
http://link.springer.com/article/10.1007/BF00248516> [Accessed 10 April 2015]
Moore, J.K. and Linthicum Jr., F.H., 2007. The Human auditory system: A timeline of
development. International Journal of Audiology [e-journal] 46 Available through:
EBSCOhost < https://www.ebscohost.com/> [Accessed 10 April 2015]
32. SID 1027821
32
Moore, D.R. and Shannon, R.V., 2009. Beyond cochlear implant: awakening deafened brain.
Nature America [e-journal] 12(6) Available Available through: EBSCOhost <
https://www.ebscohost.com/> [Accessed 8 April 2015]
Nash, A., Sharma, A., Martin, K. and Biever, A., 2007. Clinical applications of the P1 Cortical
Auditory Evoked Potential (CAEP) Biomarker. [pdf] Available at: <
www.colorado.edu/slhs/eeglab/pdfs/Nash2007.pdf> [Accessed April 4 2015]
NSC, 2006. The UK NSC recommendation on Hearing screening for newborns. [online]
Available at : <http://www.screening.nhs.uk/hearing-newborn> [Accessed 21 April 2015]
Ostroff, J.M., Brett, A. and Boothroyd, A., 1998. Cortical Evoked Response to Acoustic
Change within a Syllable. Ear and Hearing [e-journal] 19(4) Available through: Anglia Ruskin
University Library website <http://libweb.anglia.ac.uk> [Accessed 22 April 2015]
Parfect, V., 2015 Impact of Hearing Impairment. [online via internal VLE] Anglia Ruskin
University Available at: < https://vle.anglia.ac.uk/modules/2014/MOD004200/SEM2-C-
1/Content/Lecture%205.aspx> [Accessed 21 April 2015]
Ponton, C.W. and Eggermont, J.J., 2001. Of kittens and kids: altered cortical maturation
following profound deafness and cochlear implant use. Audiology and Neuro-Otology [e-
journal] 6(6) Abstract only. Available through :<
http://europepmc.org/abstract/med/11847464> [Accessed 8 April 2015]
Purdy, S.C, Kelly, A.S. and Davies, M.G., 2002. Auditory Brainstem Response, Middle Latency
Response, and Late Cortical Evoked Potentials in Children with Learning Disabilities. Journal
of American Academy of Audiology [pdf] 13 Available at: <
http://www.audiology.org/sites/default/files/journal/JAAA_13_07_03.pdf > [Accessed 19
April 2015]
Purdy, S.C., Sharma, M., Munro, K.J. and Morgan, C.L.A., 2012. Stimulus level effects on
speech-evoked obligatory cortical auditory evoked potentials in infants with normal hearing.
Clinical Neurophysiology [e-journal] 124 Available through: ScienceDirect
<http://www.sciencedirect.com> [Accessed 16 April 2015]
33. SID 1027821
33
Sharma, A., Kraus, N., McGee, T.J. and Nicol, T.G., 1997. Developmental changes in P1 and
N1 central auditory responses elicited by consonant-vowel syllables.
Electroencephalography and Clinical Neurophysiology [e-journal] 106 (6) Available through:
ScienceDirect <http://www.sciencedirect.com> [Accessed 10 April 2015]
Sharma, A., Dorman, M.F. and Spahr, A.J., 2002. A Sensitive Period for the Development of
the Central Auditory System in Children with Cochlear Implants: Implications for Age of
Implantation. Ear and Hearing [e-journal] 23(6) Available through: Anglia Ruskin University
Library website <http://libweb.anglia.ac.uk> [Accessed 17 March 2015]
Sharma, A., Martin, K., Roland, P., Bauer, P., Sweeney, M.H., Gilley, P. and Dorman, M.,
2005. P1 latency as a biomarker for central auditory development in children with hearing
impairment. Journal of American Academy of Audiology [e-journal] 16 Available through:
PubMed < http://www.ncbi.nlm.nih.gov/> [Accessed 4 April 2015]
Swink, S. and Stuart, A., 2012. Auditory long latency responses to tonal speech stimuli.
Journal of Speech, Language, and Hearing Research [e-journal] 55 Available through: Anglia
Ruskin University Library website <http://libweb.anglia.ac.uk> [Accessed 11 April 2015]
34. SID 1027821
34
Appendix 2
Ethics approval
Dear Nauris,
Project title: Evaluation of central auditory development using cortical
auditory evoked potential (CAEP) in hearing impaired
children with cochlear implants
Application number: VHS DREP 0415-22
Principal Investigator: Nauris Veits
Supervisor: Fei Zhao
Decision:
The Chair of the Vision and Hearing Sciences Departmental Research Ethics Panel (VHS
DREP), acting on behalf of the Committee, has agreed to grant ethical approval for your
research, subject to ratification by the Faculty Research Ethics Panel (FREP). Under the
terms of Anglia Ruskin University’s Policy and Code of Practice for the Conduct of Research
with Human Participants, approval is for a period of one year from 30/04/2015
Please Note:
It is your responsibility to ensure that you comply with Anglia Ruskin University’s Policy and
Code of Practice for Research with Human Participants, and specifically:
The Participant Information Sheet and Participant Consent Form should be on Anglia Ruskin
University headed paper.
For online surveys it is recommended that the researcher turns off the IP logging
software to ensure secure communication between the survey taker and server.
Any substantial amendments should be submitted to the Committee, should there be
any changes to your research. You cannot implement such changes until you have
received approval from FREP for them.
You must adhere to the procedure for reporting adverse events and incidents.
You must comply with the Data Protection Act (1998) and any other legislation relevant
to your research. You must also ensure that you are aware of any emerging legislation
relating to your research and make any changes to your study (which you will need to
obtain ethical approval for) to comply with this.
You must obtain any further ethical approval required from the organisation or country
(if not carrying out research in the UK) where you will be carrying out the research.
Please ensure that you send the FREP Secretary copies of this documentation.
35. SID 1027821
35
You must comply with any laws of the country where you are carrying the research out
(if these conflict with any aspects of the ethical approval given, please notify FREP prior
to starting the research).
You must adhere to any professional codes of conduct relating to research or
requirements from your funding body (please note that for externally funded research, a
project risk assessment must have been carried out prior to starting the research).
You are responsible for notifying the FREP Secretary when your study has ended.
Information about the above can be obtained on our website
at: http://web.anglia.ac.uk/anet/rdcs/ethics/index.phtml/ and
or http://www.anglia.ac.uk/ruskin/en/home/faculties/fst/research0/ethics.html
Please also note that your research may be subject to random monitoring by the
Committee.
Please be advised that, if your research has not been completed within one year, you will
need to apply to our Faculty Research Ethics Panel for an extension of ethics approval prior
to the date your approval expires. The procedure for this can also be found on the above
website.
Should you have any queries, please do not hesitate to contact me.
I would like to wish you the best of luck with your research.
Kind regards
Jane
Jane Somers
Administrator for the Vision & Hearing Sciences Departmental Research Ethics Panel
Faculty of Science & Technology
Anglia Ruskin University
Cambridge
0845 196 2116
cc: supervisor
