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EVALUATION OF CENTRAL AUDITORY DEVELOPMENT USING CORTICAL AUDITORY EVOKED

POTENTIAL IN HEARING IMPAIRED CHILDREN WITH COCHLEAR IMPLANTS

Mod 002497

This dissertation is submitted in part fulfilment of the BSc Honours degree programme regulations in

the Department of Vision and Hearing, Anglia Ruskin University.

Word count 6000

Author: Nauris Veits

May 2015

Acknowledgement

I would like to thank all Anglia Ruskin University staff who have been with us last nine

months. You have been fantastic!

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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!

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..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

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

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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

Table of contents

Introduction 1

P1-N1-P2 complex 6

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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

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.

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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,

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

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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).

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Figure 1 (reprinted from

Burkard, et.al. 2007)

Auditory Evoked Potentials

in relation of the auditory

pathway.

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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).

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Figure 3 (reprinted from Sharma, et.al, 2001) P1 latencies in normal hearing individuals. Shortening of latency as auditory cortex matures.

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).

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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.

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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

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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

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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.

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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.

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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

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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.

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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.

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Mean latency (ms)/ avg. age 2y5m

0

50

100

150

200

250

300

350

313.8

259.7

177.8

115

Activation3 months6 monthsNormal latency for 2y5m

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.

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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

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Activation 3 m 6 m0

50

100

150

200

250

300

350

400

290

163

99

305.5

280

150

365

311

275

Min 1y 2mMed 2y 4mMax 4y 3m

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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) Change of amplitude

after switch-on of the CI. Early and middle

implanted group has reduction of amplitude

after 3 months however has slight increase

of amplitude after 6 months. Late implanted

group has steadily reduction of amplitude of

P1 after 3 and 6 months.Mean amplitude (µs) ...

0

1

2

3

4

5

6

4.85 µs

2.46 µs

3.05 µsActivation3 m6 m

Activation 3 m 6 m0

1

2

3

4

5

6

7

8

9

10

1.58 µs1.12 µs 1.27 µs

4.72 µs

2.38 µs

3.32 µs

8.77 µs

5.13 µs

4.92 µsMin 1y2mMed 2y 4mMax 4y3m

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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.

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20

Group 1/ mean age 3.2 years Group 2/ mean age 10.4 years0

50

100

150

200

250

300

156.2

267.7

119.7

232.6

110

70

6 months post-implant12 months pots-implantAverage latency for normal hearing subject

Group 1/ mean age 3.2 years Group 2/ mean age 10.40

1

2

3

4

5

6

7

8

9

10

7.17

3.75

9.49

5.78

6 months post-implant12 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

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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.

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Figure 10 (reprinted from Sharma, et.al 2005) Subject 1

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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.

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

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.

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).

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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

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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.

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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.

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 yearsGroup 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

Table 2 (Summary of test subjects and recording methodology)

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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).

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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.

Figure 14 (reprinted from Sharma, et.al. 2007) demonstrate CI implant influence to P1 latency

depending on age of 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.

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.

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(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

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shorter and synthesised stimulus /m/, /g/, and /t/. Simpler stimulus will elicit greater

amplitude compared more complex syllable (Ostroff, et.al, 1998).

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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.

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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 0415-22Principal Investigator: Nauris VeitsSupervisor: 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 soft-ware 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 re-ceived 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.

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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 require-ments from your funding body (please note that for externally funded research, a pro-ject 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

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