Clinical Neurophysiology 148 (2023) 76–92

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Clinical Neurophysiology
journal homepage: www.elsevier.com/locate/clinph

Mismatch negativity as a marker of music perception in individual

cochlear implant users: A spike density component analysis study
Niels Trusbak Haumann a,⇑, Bjørn Petersen a, Anne Sofie Friis Andersen a, Kathleen F. Faulkner b,
Elvira Brattico a, Peter Vuust a
a
Center for Music in the Brain, Department of Clinical Medicine, Aarhus University and The Royal Academy of Music, Aarhus/Aalborg, Universitetsbyen 3, 8000 Aarhus C, Denmark
b
Oticon Medical, Kongebakken 9, 2765 Smørum, Denmark

h i g h l i g h t s

MMN measurements predict individual cochlear implant (CI) users’ behavioral music perception.

MMN is detected in fewer CI users when sound deviants are of smaller magnitude.

New spike density component analysis method enables more accurate diagnostics than preceding state-of-the-art.

a r t i c l e i n f o a b s t r a c t

Article history: Objective: Ninety percent of cochlear implant (CI) users are interested in improving their music percep-
Accepted 24 January 2023 tion. However, only few objective behavioral and neurophysiological tests have been developed for trac-
Available online ing the development of music discrimination skills in CI users. In this study, we aimed to obtain an
accurate individual mismatch negativity (MMN) marker that could predict behavioral auditory discrim-
Keywords: ination thresholds.
EEG
Methods: We measured the individual MMN response to four magnitudes of deviations in four different
Audiology
Music
musical features (intensity, pitch, timbre, and rhythm) in a rare sample of experienced CI users and a con-
Cochlear implants (CI) trol sample of normally hearing participants. We applied a recently developed spike density component
MMN analysis (SCA), which can suppress confounding alpha waves, and contrasted it with previously proposed
SCA methods.
Results: Statistically detected individual MMN predicted attentive sound discrimination ability with high
accuracy: for CI users 89.2% (278/312 cases) and for controls 90.5% (384/424 cases). As expected, MMN
was detected for fewer CI users when the sound deviants were of smaller magnitude.
Conclusions: The findings support the use of MMN responses in individual CI users as a diagnostic tool for
testing music perception.
Significance: For CI users, the new SCA method provided more accurate and replicable diagnostic detec-
tions than preceding state-of-the-art.
Ó 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open
access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

1. Introduction
A main goal for 30–37 % of cochlear implant (CI) users is to
restore abilities to listen to music with the CI device (Kohlberg
et al., 2014, Migirov et al., 2009). However, for CI users, music per-
ception and enjoyment from music is more challenged and varied
than in normally hearing individuals, despite music is a factor that
⇑ Corresponding author at: Center for Music in the Brain, Department of Clinical
Medicine, Aarhus University and The Royal Academy of Music, Aarhus/Aalborg,
Universitetsbyen 3, 8000 Aarhus C, Denmark.
E-mail address: niels.haumann@clin.au.dk (N.T. Haumann).
often heightens the perceived quality of life, even with only resid-
ual hearing abilities (Dritsakis et al., 2017, Fuller et al., 2022,
Lassaletta et al., 2007). Indeed, a study showed that 90 % of CI users
are interested in rehabilitative programs for improving their music
experience (Gfeller et al., 2019). Also, music stimuli can be applied
to test general aspects of listeners’ sound discrimination ability by
using stimuli that most people find enjoyable (Dritsakis et al.,
2017, Lassaletta et al., 2007). Therefore, it is pertinent to identify
accurate diagnostic tools for testing the individual variation in CI
users’ music perception (Hahne et al., 2016, Koelsch et al., 2004,
Petersen et al., 2020, Petersen et al., 2015, Sandmann et al., 2010,
Timm et al., 2014, Torppa et al., 2012).

https://doi.org/10.1016/j.clinph.2023.01.015
1388-2457/Ó 2023 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
N.T. Haumann, Bjørn Petersen, A.S. Friis Andersen et al.
Electrophysiological tests on auditory brain function provide
relatively fast, objective, and non-invasive measures to comple-
ment behavioral tests and questionnaires. They are especially
advantageous when verbal or written tests cannot be adopted such
as for infants and young children (Cone-Wesson, 2003, Gibson
et al., 2009, Gilley et al., 2008, Golding et al., 2007, Näätänen
et al., 2012, Näätänen et al., 2017, Nelson et al., 2008, Ponton
et al., 2000, Sharma et al., 2002, Silva et al., 2017, Skoe and
Kraus, 2010, Wang et al., 2015, Zhang et al., 2011). Among those
tests, the Wave V component of the auditory brainstem response
(ABR) can be applied to predict the pure tone hearing threshold
at specific frequencies (Gibson et al., 2009, Skoe and Kraus, 2010,
Wang et al., 2015). However, when ABR tests are conducted with
a hearing aid or CI device switched on, the sound stimulus is lim-
ited to a duration of only a few milliseconds, to avoid overlap
between the electrical stimulation artifact from the hearing device
and the measured wave V occurring at a latency of approximately 5
milliseconds.
Cortical auditory evoked potentials (CAEPs), such as the audi-
tory thalamo-cortical P1 component, are becoming popular mea-
sures for testing hearing thresholds for temporally-spectrally
complex sounds, which are relevant in everyday language learning
and understanding (Gilley et al., 2008, Mehta et al., 2019, Sharma
et al., 2002, Silva et al., 2017). The electrical stimulation artifacts
from the hearing device can be supressed from the measures of
the CAEPs, e.g., by means of independent component analysis
(ICA) (Gilley et al., 2006). A limitation of the P1 test is that it is cur-
rently uncertain whether it can be applied to test listeners’ ability
to distinguish between sounds, which is an important prerequisite
for understanding their meaning. Indeed, everyday sounds in
music and language consist of continuous acoustical feature tran-
sitions, which the listener must be able to hear, discriminate, and
learn (Iverson et al., 2006, Loizou et al., 1998, Shestakova et al.,
2004).
For testing auditory discrimination in a clinical context, various
CAEP responses have been considered, such as the thalamo-cortical
middle latency Nb and Pb responses (Althen et al., 2016) and the
cortical long latency P1 (Gilley et al., 2005, Munivrana and
Mildner, 2013), N1 (Finke et al., 2016, Munivrana and Mildner,
2013, Sandmann et al., 2015, Zhang et al., 2011), P2 (Han et al.,
2016, Munivrana and Mildner, 2013, Zhang et al., 2011), mismatch
negativity (MMN) (Näätänen et al., 2012, Näätänen et al., 2017,
Ponton et al., 2000), P300 (Alniacik and Akdas, 2019, Finke et al.,
2015, Groenen et al., 2001, Munivrana and Mildner, 2013, Van
Yper et al., 2020), and N400 responses (Kallioinen et al., 2016).
Among these, the MMN is a promising candidate, because the audi-
tory MMN generally reflects discrimination ability for sounds –
either verbal, non-verbal, or musical – in health, pathology, and
across the lifespan (Näätänen et al., 2017). Also, the MMN response
does not require the listener to attend to the auditory stimuli or to
perform a demanding task, which makes MMN suitable also for
infants and young children in addition to adults. The auditory
MMN is an automatic brain response to an infrequent and rare
sound after a repeated and more expected standard one
(Näätänen et al., 2017). The acoustical difference between the stan-
dard and deviant sound must be above the just-noticeably differ-
ence threshold to evoke an MMN (Näätänen et al., 2017, Rahne
et al., 2014).
For CI users, the MMN has been recorded to study even residual
discrimination of spoken language (Kraus et al., 1993, Lonka et al.,
2004, Singh et al., 2004), and musical sounds (Hahne et al., 2016,
Koelsch et al., 2004, Lonka et al., 2013, Petersen et al., 2020,
Petersen et al., 2015, Rahne et al., 2014, Sandmann et al., 2010,
Timm et al., 2014, Torppa et al., 2018, Torppa et al., 2014, Torppa
et al., 2012, Wable et al., 2000, Zhang et al., 2013). The musical
multi-feature (MuMuFe) paradigm (Vuust et al., 2011) was devel-
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Clinical Neurophysiology 148 (2023) 76–92
oped for investigating MMN responses to sound differences in
spectral-temporal features presented in a musical context. With
the latest development of the MuMuFe CI paradigm, statistically
significant MMN responses were successfully obtained in a group
of CI users for all tested features (intensity, pitch, timbre, rhythm)
on at least one out of four deviant magnitude levels (Petersen et al.,
2020). These findings support that MMN is a promising marker of
music discrimination in CI users.
The last 30 years of research on MMN responses in individual
listeners has, however, not reached sufficient accuracy for clinical
application (Bishop and Hardiman, 2010, Dalebout and Fox, 2001,
Escera and Grau, 1996, McGee et al., 1997, Näätänen et al., 2017,
Paukkunen et al., 2011, Pekkonen et al., 1995, Uwer and von
Suchodoletz, 2000) despite of the implementation of paradigms
aimed at clinical practice such as the multi-feature versions. For
instance, the least accurate MMN detection performance has been
observed with visual inspection by EEG experts, where confound-
ing cortical sources, such as alpha waves, have been mistakenly
identified as MMN in 63 % cases when no MMN was present
(McGee et al., 1997), which means that more than every second
patient would incorrectly pass MMN testing without existing
sound discrimination problems being identified. Proposals have
been made to improve the accuracy of the individual MMN analy-
sis (Bishop and Hardiman, 2010, Dalebout and Fox, 2001, Kalyakin
et al., 2009, McGee et al., 1997, Näätänen et al., 2017, Ponton et al.,
1997, Rahne et al., 2008, Torppa et al., 2012). The most accurate
results have been achieved with individual-level statistics, with
88.2 % correct detections of MMN absence for indiscriminable
sounds and 82.4 % correct detections of MMN presence for discrim-
inable sounds (Bishop and Hardiman, 2010). A main challenge with
measurement of individual evoked responses is the confounding
cortical sources (Scharf et al., 2022), such as alpha waves, which
also interfere with the individual MMN measurements
(Haumann et al., 2020).
In this study, we test whether the issues specified above,
which all limit the accuracy of the individual MMN and its pre-
dictive value in assessing the individual music discrimination
skills in CI users, might be overcome by our very recently
method that allows decomposing the overlapping large-scale
cortical activity with spike density component analysis (SCA)
(Haumann et al., 2020). Empirical and simulation studies have
consistently confirmed that SCA is accurate in separating large-
scale bioelectromagnetic cortical activity into sparse temporal
shapes with distinct scalp topographies from both adults
(Haumann et al., 2020) and children (Bruzzone et al., 2021). Pre-
vious studies on normally hearing young adults and computer-
simulated EEG (Haumann et al., 2020) have shown that SCA is
more accurate than spatial principal component analysis (PCA)
and ICA in isolating individual MMN from confounding cortical
interfering sources, such as alpha waves.
In sum, the aim of the present study is to obtain accurate indi-
vidual markers of central auditory function in CI users that could
predict their individual behavioral music discrimination thresh-
olds. We hypothesized that statistical detection of the individual
MMN response would predict individual behavioral music discrim-
ination ability. This was followed up with supplementary assess-
ments of the validity and precision of the hypothesized MMN-
behavior relationship. Also, since smaller deviant magnitudes
should extend below the discrimination thresholds of individual
listeners, we tested whether MMN was detected in fewer individ-
uals when the deviant magnitudes were smaller. Moreover, we
assumed that the common dissimilarity between CI users and NH
groups might be observed for pitch that is most technically chal-
lenging in CI listening. All these findings were obtained with a
new SCA statistics procedure, therefore, it was relevant to prove
that each option in this new procedure was optimal in terms of
N.T. Haumann, Bjørn Petersen, A.S. Friis Andersen et al. Clinical Neurophysiology 148 (2023) 76–92

accuracy and replicability (see the Methods section and Appen-
dices for further details).
2. Methods
2.1. Participants
This study is based on a re-analysis of 312 cases of averaged
MMN waveforms from repeatedly measured cochlear implant
(CI) users and 424 cases from normally hearing controls, previously
introduced in Petersen et al. (2020). A group of eleven experienced
older CI users with an average of 7.0 years CI experience (range 1–
14 years) and average age of 56.1 years (range 34–77 years) (nine
women) participated in the study. Nine CI users had a high CI out-
come with reported ability to speak on the phone (for individual
details, see Table 1). The average duration of deafness prior to
receiving the CI was 23.6 years (range 0 to 56), nine had one CI
implant in an ear (unilateral implant) and two in both ears (bilat-
eral), and six used the left ear for testing whereas five used the
right ear. Four CI users in addition used a hearing aid in the ear
opposite to the ear with the implant. As a control group partici-
pated fourteen older participants with normal hearing and an aver-
age age of 63.4 years (range 56–77), similar to the age of the CI
group. None of the participants had an academic background in
music, and they reported not to be professional or amateur musi-
cians and to have less than 5 years formal singing or instrument
training. The study was conducted in accordance with the Helsinki
declaration and approved by the Research Ethics Committee of the
Central Denmark Region. All participants provided written
informed consent.
2.2. Stimuli
The cochlear implant musical multi-feature (CI MuMuFe) mis-
match negativity (MMN) paradigm (Petersen et al., 2020) was
based on a four-tone Alberti bass melody played in four different
keys (C, Eb, Gb, and A) (listen to an excerpt of the stimuli in the
Supplementary Material audio file). It contained tones in the mid-
dle register range from Ab3 (208 Hz) to E5 (659 Hz). All tones had a
duration of 200 ms (except rhythm deviants), a rise and fall time of
18 ms, and were followed by a silent interstimulus interval of 5 ms.
MMN responses to tones were tested on four fundamental features
in music: intensity, pitch, timbre, and rhythm. Deviant tones evok-
ing MMN for each sound feature were inserted at the third tone in
the Alberti Bass pattern with one out of four deviant magnitudes:
extra-large (XL), large (L), medium (M), or small (S). MMN to inten-
sity deviants were created by decreasing the intensity of the tone
by 12 (XL), 9 (L), 6 (M), or 3 (S) decibels (dB). Pitch deviants were
inserted by lowering the pitch by eight semitones (–37 % Hz) (XL),
three semitones (–16 % Hz) (L), two semitones (–11 % Hz) (M), or
one semitone (–6% Hz) (S). Timbre deviants were created with an
exchange of a regular piano sound to a guitar (XL), trumpet (L),
blues piano (M), or bright piano (S) sound. Finally, rhythm deviants
were inserted as earlier onsets of the third note by 155 ms (XL),
103 ms (L), 52 ms (M), or 26 ms (S), (while at the same time short-
ening the second note to avoid sound overlap and lengthening the
third note accordingly to avoid a silent gap).
The sixteen deviants occurred with equal probability (6 %) on
the third tone in the repeated melody. All deviant tones and
changes of key occurred in a pseudo-randomized order, where
the same deviant or key was not repeated consecutively. (The
change of key occurred after three repetitions of each of the 16
deviant conditions, and the first tone at each key change was
excluded from subsequent analysis.) To reduce the required EEG
recording time by 50 %, the so-called ‘‘no-standard” paradigm uses
a common and well-tested procedure of applying the repeated
tones 1, 2, and 4 in the Alberti Bass pattern as standard tones, as
an alternative to standard tones on the third tone in every second
tone-pattern, with either option resulting in similar MMN differ-
ence waveforms (e.g., Bonetti et al., 2017, Kliuchko et al., 2019,
Kliuchko et al., 2016, Pakarinen et al., 2010). In total there was
2304 stimulus trains (i.e., groupings of four tones) and 48 key
changes.
2.3. EEG procedure
The experiment was conducted at the EEG lab facilities of Aar-
hus University Hospital. EEG was recorded at a sampling rate of
1000 Hz in an electrically and acoustically shielded room with a
BrainAmp amplifier system (Brain Products, Gilching, Germany).
Electrodes were placed in a 32-electrode cap according to the
international 10/20 system. It was ensured that electrode impe-
dances were < 25 kX. An electrooculogram (EOG) was recorded
with electrodes beside and above the left eye. FCz was applied as
an initial reference electrode. The auditory stimuli were played
in mono at a 44.1 kHz sampling rate. During EEG recordings partic-
ipants were instructed to ignore the auditory stimuli and focus on
a movie in which the audio was muted. For all participants, the
sound level was individually adjusted to a comfortable level from
a defined starting point of 65 dB SPL. The total EEG recording time
was approximately 35 min.
2.4. EEG preprocessing
The EEG data were preprocessed as in Petersen et al. (2020) by
using the FieldTrip Toolbox for Matlab (Oostenveld et al., 2011) for
1 Hz high-pass, 25 Hz lowpass filtering, independent component
analysis (ICA) for suppression of eye movement and cochlear

Table 1
Demographic and clinical characteristics of the 11 experienced cochlear implant (CI) users. Hearing aid: the participant wears a hearing aid on the ear contralateral to the
implanted ear. Telephone ability: the participant reports ability to communicate via telephone via CI only or both CI and hearing aid. This table is reproduced from Petersen et al.
(2020). Information about the type of CI device has been added when available.

Group Age at project Duration of deafness prior CI experience Number of Side of implant used Type of CI device Hearing Telephone
ID start (years) to CI (years) (years) implants for tests used for tests aid ability
CI01 65–70 32 7 1 L Cochlear, Kanso Yes Yes
CI02 45–50 36 10 1 L Cochlear, N5 CP810 No Yes
CI03 50–55 20 5 1 R Cochlear, N6 CP910 No Yes
CI04 55–60 17 9 2 R Cochlear, N6 CP910 No Yes
CI05 60–65 56 4 1 L Cochlear, N6 CP920 No Yes
CI06 60–65 10 14 2 L Cochlear, N5 No Yes
CI07 45–50 17 7 1 R Cochlear, N6 CP920 Yes Yes
CI08 65–70 55 8 1 R Cochlear, N6 CP920 No No
CI09 75–80 8 4 1 L Cochlear No No
CI10 35–40 9 1 1 R Cochlear Yes Yes
CI11 35–40 0 8 1 L Cochlear Yes Yes
Mean 56.1 23.6 7.0

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N.T. Haumann, Bjørn Petersen, A.S. Friis Andersen et al.
implant (CI) artifacts, and re-referencing the channel waveforms to
the average reference across channels. The individual EEG data was
segmented into 144 trials for each of the 16 types of deviant tones
and 6288 standard tone trials. Moreover, 16 ‘‘false deviant” wave-
forms contrasting the 16 true deviant conditions were extracted
based on carefully matched subsets of the standard trials, which
contain representative residual EEG noise and no MMN for indis-
tinguishable repeated standard tones (cf. Bishop and Hardiman,
2010) (see Appendix A for further details). For the individual-
level spike density component analysis (SCA) statistics no baseline
correction was applied by default. Instead, we applied a spatiotem-
poral SCA filter, which attenuates all other components than the
tested component, and thereby also suppresses any interfering
components occurring before or after the sound onsets. Remaining
noisy trials exceeding -/+ 100 lV were automatically rejected.
After the trial rejections, for the CI users, there were on average
143.5 deviant trials (range: 136–144) and 6244.3 standard trials
(range: 6049–6288), and for the normally hearing, on average
143.6 deviant trials (range: 135–144) and 6252.7 standard trials
(range: 6048–6288) (all reported deviant trials includes ‘‘false
deviant” trials). Finally, the average standard trials were subtracted
from the average deviant (or ‘‘false deviant”) trials to isolate the
individual MMN (or ‘‘false MMN”) difference waveforms
(Näätänen et al., 2017). We followed a common procedure of ana-
lysing difference waveforms at the individual level for automatized
MMN detection (Bishop and Hardiman, 2010, McGee et al., 1997)
by subtracting the mean standard waveform across trials from
each deviant trial to isolate the individual MMN at the single
trial-level.
2.5. Behavioral auditory discrimination test
In addition to the individual MMN testing, all participants com-
pleted a three-alternative forced choice test, where the task was to
identify which one out of sets of three melodic patterns contained
a sound deviant (Petersen et al., 2020). This test resulted in scores
of 0 %, 17 %, 33 %, 50 %, 67 %, 83 %, or 100 % correct answers (with
chance level at 33.3 %), where higher scores reflect more reliable
sound discrimination. This behavioral test reflects the sound dis-
crimination ability for the same music parameters and levels of
magnitude as presented in the MMN paradigm measured with
EEG.
2.6. Individual-level EEG statistics
For clinical applications, it would be important to statistically
determine whether the individual MMN can be interpreted as ab-
sent (i.e., either absence or presence interpretation in, e.g., Carter
et al., 2010, Golding et al., 2007), because this can indicate a hear-
ing impairment and a need to refer a patient to further testing or
treatment (cf. Kuki et al., 2013, Schmidt et al., 2001). If the individ-
ual MMN is interpreted as absent for a sound deviance that would
trigger a measureable MMN in a normally hearing population (e.g.,
MMN to a pitch deviant at a level of 8 semitones difference), then
the individual MMN could be applied as a diagnostic tool
indicating an auditory discrimination disorder (e.g., impaired pitch
discrimination). Statistical detection of individual MMN pres-
ence would be less clinically important because it means that a
patient would pass MMN diagnostics, indicating an ability to dis-
tinguish between specific sounds. Therefore, we define the test
sensitivity as the percentage correct interpretation of individual
MMN absence for indistinguishable sounds (cf. Kuki et al., 2013,
Schmidt et al., 2001). We define the test specificity as the percent-
age correct detection of individual MMN presence for distinguish-
able sounds (cf. Kuki et al., 2013, Schmidt et al., 2001). Whether the
individual MMN was interpreted as either absent or present was
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Clinical Neurophysiology 148 (2023) 76–92
automatically determined by an SCA statistics algorithm described
below.
2.6.1. Spike density component analysis (SCA) decomposition
As a first step, in order to suppress confounding alpha waves
disturbing the MMN waveform, the individual averaged difference
waveforms were decomposed into spike density component anal-
ysis (SCA) components (Haumann et al., 2020) (Fig. 1 A) (FieldTrip
compatible Matlab functions for SCA decomposition and SCA
statistics are available at https://github.com/nielsthaumann/sca).
SCA is a type of fast, automatic, non-supervised machine learning
method, which optimizes a model predicting the individual bio-
electromagnetic activity of large-scale cortical neural assemblies
from individual EEG or MEG measurements. SCA implements a
constraint based on the assumption that the bioelectromagnetic
source of a ‘‘spike density”, or neural current, generated in a
large-scale cortical neural assembly (10,000 neurons) approxi-
mates a Gaussian shape over time (the term ‘‘spike density” is
derived from the ‘‘spike train” concept for describing the peristim-
ulus time histograms measured on single neurons). It was verified
that the Gaussian temporal shapes explain most variance in scalp-
recorded EEG and MEG, whereas sine, gamma, and asymmetrical
Gaussian halves shapes explained significantly less variance, and
it was confirmed that the Gaussian shapes specifically modeled
most of the neural activity originating within the scalp and could
not model non-neural external signals, such as eye movement arti-
facts (Haumann et al., 2020). It should also be noted that the SCA
method assumes that the signal of interest (i.e., the MMN) shows
one or more peaks in time at a signal-to-interference-and-noise
ratio larger than 1 (i.e., in at least one electrode at one time point
the MMN should have larger amplitude compared to confounding
alpha waves) (Haumann et al., 2020). These assumptions seem
realistic in the present study for the separation of MMN from con-
founding alpha waves in pre-processed averaged EEG waveforms,
because the EEG is time-locked at tone stimulus onsets and
thereby confounding alpha waves are partially distributed in phase
and suppressed in amplitude.
2.6.2. Region of interest constraints
To ensure that the individual pre-attentive MMN was detected,
and not other clearly differing responses such as following P3(a,b)
responses, and also to ensure fast computational processing of the
statistical analyses, we applied region of interest (ROI) constraints
(Bruzzone et al., 2021). Only SCA components with a negative peak
in the frontal half of the EEG channels within a relevant MMN
latency range were tested statistically (Fig. 1B). Since the MMN
latency is more varied in patients, older listeners, and children than
in normally hearing young adults, it is common to apply a rela-
tively broad individual MMN latency time-window ranging
approximately between 0–450 ms in clinical individual MMN liter-
ature (Dalebout and Fox, 2001, Escera and Grau, 1996, McGee et al.,
1997, Näätänen et al., 2017, Ponton et al., 1997, Taylor et al., 2017).
Here we constrained the MMN peak latency to between 75–
300 ms.
2.6.3. Trial-level spatiotemporal SCA filter
The inter-trial variance originating from interfering SCA compo-
nents and EEG channel noise was reduced by using the SCA compo-
nent as a spatiotemporal filter (cf. Li et al., 2008) (Fig. 1C). The
spatiotemporal filter was applied to each trial by multiplying the
trial by the tested SCA component to obtain a weighted average,
which reduced signals unrelated to the tested SCA component:
pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi
trialf ¼ sgnðtrialW i xi ÞÞ  jtrialW i xi j (1)where trialf is the fil-
tered multichannel trial waveform, trial is the multichannel trial
waveform, Wi is the component channel weights, and xi is the com-
N.T. Haumann, Bjørn Petersen, A.S. Friis Andersen et al. Clinical Neurophysiology 148 (2023) 76–92

p< p p

Fig. 1. Overview of the steps in the spike density component analysis (SCA) statistics procedure. (A) Single-participant EEG difference waveforms decomposed into neural
activity with independent scalp distributions (left) and time-courses (right). (B) Constraining the peak electrodes, polarity, and latency reveals candidate MMN components.
(C) The spatiotemporal filter (black color) efficiently focuses the across-trial EEG variance on an MMN candidate component to be statistically tested (interquartile range
shown in shaded color; comparison to no filtering shown in blue color). (D) Across-trial amplitude histograms. (E) An automatic detection of an SCA component clearly
representative of individual-level MMN (shown with shaded 99% confidence intervals uncorrected for multiple testing).

80
N.T. Haumann, Bjørn Petersen, A.S. Friis Andersen et al.
ponent waveform. The formula ensured that the tested SCA com-
ponent amplitude was always positive-valued. (Also, filtering an
ideal trial waveform without cross-trial variance, trial = Wi xi,
results in the same (positive-valued) output as the input, trialf=|
trial|.) Since the SCA component amplitude is always positive-
valued after the spatiotemporal filtering, an area measure was
derived for each trial simply as the summed amplitude over all
channels and time samples (for more details, see Appendix B).
The distribution of area measures across trials was then submitted
to individual-level SCA statistics.
2.6.4. Individual-level SCA statistics
In previous work, the SCA components were considered signif-
icant, if they correlated with a specific template, e.g., a grand-
average template (Haumann et al., 2020). However, the template
match method assumed that the individual latency or topography
did not deviate significantly from the specific template, which is
violated in heterogenous samples, particularly in developmental
or clinical samples. These limitations were solved by proposing
that each SCA component could be statistically tested based on
the individual-level trial distribution (Bruzzone et al., 2021). For
the present study, we solved two remaining issues. First, we intro-
duce a simple and standardized significance p-threshold, instead of
a first significance threshold for SCA component correlation with
sub-averages, and a second significance threshold for determining
SCA component consistency across sub-averages (Bruzzone et al.,
2021). Second, we increase the computational speed by applying
one statistical test on each SCA component, instead of previous
100 statistical tests for each SCA component’s correlation with
100 sub-averages. For statistical inference, the distribution of the
SCA component area measures across trials was tested with a
one-sample t-test (Fig. 1D). If the t-test resulted in a p-value smal-
ler than the p-threshold, then the null-hypothesis that the SCA
component is part of the error distribution centred on the baseline
at 0 lV was rejected (Fig. 1E), otherwise, the null-hypothesis was
retained.
To verify the effects of choosing the proposed optimal SCA
statistics on the diagnostic accuracy and the control of the replica-
bility of the individual-level results, the tailoring of the individual-
level SCA statistics was compared to common nonoptimal options.
Choosing common but nonoptimal options led to significantly
lower diagnostic accuracy and lower control of the replicability
of the individual-level results (all methodological comparisons
and results are explained in detail in Appendix C).
Finally, the state-of-the-art ‘‘t-cluster” method was tested. For
valid comparison with SCA statistics, the same ROI constraints
(section 2.6.2) were applied for t-clusters as for SCA statistics. At
each time sample, one-sample t-tests were conducted across trials,
and the t-cluster p-values were obtained as the maximum p-value
over 32 ms consecutive time samples (8 at 250 Hz) (Bishop and
Hardiman, 2010). If the p-value remained smaller than the p-
threshold across 32 ms consecutive time samples, the t-cluster
was interpreted as significant, otherwise non-significant (Bishop
and Hardiman, 2010).
2.7. Statistical evaluation of the prediction of behavioral auditory
discrimination based on the individual MMN
All subsequent statistical analyses were conducted with the
IBM SPSS v27 software package (IBM, Armonk, New York, USA).
The CI and the NH groups were investigated separately. As is com-
mon in classification studies where the EEG is applied to predict a
certain behavioral outcome, the repeated measures for the 16
stimulus conditions from each participant were treated as inde-
pendent observations, where each observation depends on noise
in the EEG trials and in the behavioral tests (e.g., Amin et al.,
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Clinical Neurophysiology 148 (2023) 76–92
2017, Golz et al., 2016, Perez-Valero et al., 2021). The advantage
of this procedure is that the evaluations reflect the performance
of the individual-level MMN test on more deviant features and
magnitudes, as well as on measures from different participants,
which is relevant for clinical applications with individual CI users
where consistent individual-level results are important.
2.7.1. MMN as a marker of auditory discrimination thresholds in
individual CI users
2.7.1.1. Diagnostic accuracy. The diagnostic accuracy was analyzed
with a receiver operating characteristic (ROC) curve based on vary-
ing the p-threshold on 100 equal logarithmic steps from 10-34 to 1.
The test sensitivity in the ROC analysis was based on the ‘‘false
MMN” with indistinguishable sounds. The sensitivity was defined
as the percentage correct retainment of the null-hypothesis, mean-
ing that there was no individual MMN, and indicating inability to
discriminate between the sounds. Also, an individual should be
able to pass the MMN testing with an outcome that does not moti-
vate for treatment. This is indicated by the test specificity, which
was estimated as the percentage correct individual MMN detec-
tions for the cases where the individual study participants scored
above chance level on the behavioral sound discrimination test.
The balanced accuracy was calculated as the sum of the sensitivity
and specificity divided by two. The area under the curve for the
sensitivity and specificity was compared to the random chance
level diagnostic outcome with the Wilcoxon statistic as imple-
mented in SPSS (Coelho and Braga, 2015). The ROC curves were
visualized with bias-corrected and accelerated 95 % confidence
intervals with the Matlab function fitglm (using the binomial distri-
bution logistic regression option) and the Matlab function per-
fcurve (applying 1000 bootstrap permutations).
2.7.1.2. Validity. Supplementary to the main hypothesis on diag-
nostic accuracy, the validity and precision of the individual
MMN-behavior relationships were further assessed. Initial inspec-
tion suggested that the assumption of a continuous (linear or non-
linear) relationship between the individual MMN peak amplitude
measured within the region of interest (defined above) and the
behavioral hit rate was violated. Therefore, it was considered inap-
propriate to model a unit-wise change in the MMN amplitude in
lV per change in the behavioral score in percentage hit rate.
Instead, we tested whether the individual MMN amplitude was
lower when the behavioral discrimination was not detected (at
chance level or lower) compared to detected (above chance level).
Due to unequal sample-sizes, this comparison was tested with the
Welch’s test. A comparison was also made with the Welch’s test to
assess whether the individual MMN peak latency measured within
the region of interest (defined above) was longer for absent than
detected behavioral discrimination. Further, the behavioral hit rate
might be lower when the individual MMN was not detected com-
pared to detected, also assessed with the Welch’s test.
The above assessments pointed towards the common observa-
tion that the individual MMN can be detected when behavioral dis-
crimination is absent (Näätänen et al., 2017), and behavioral
detection can also be present when individual MMN is not
detected (Bishop and Hardiman, 2010). It was investigated
whether the common occasional MMN-behavior dissociations
might indicate different discrimination thresholds between the
MMN and behavioral tests. This assumption was tested with Pear-
son’s chi-squared tests comparing the percentage of individual
MMN detections against behavioral detections for each group
and each stimulus condition.
2.7.1.3. Precision. To further clarify the reason of the occasional
MMN-behavior dissociations, logistic regression was applied to
test a measurement error hypothesis: that the percentage missing
N.T. Haumann, Bjørn Petersen, A.S. Friis Andersen et al.
individual MMN or behavioral detections would increase when the
deviant magnitudes decrease. I.e., when the deviant magnitude
approaches the individual discrimination threshold more measure-
ment errors would be expected, which would be indicated by more
frequent incongruent individual MMN compared with behavioral
test outcomes (where either individual MMN or behavioral dis-
crimination is detected but not both). Finally, it was evaluated
whether the MMN and behavioral tests were equally precise. This
was assessed with the Mann-Whitney U test for inferring whether
the number of missing individual MMN in comparison to behav-
ioral detections were equally distributed over the deviant
magnitudes.
2.7.1.4. Correlation with music appreciation and clinical factors. Rela-
tionships between the individual MMN amplitude and latency at
the Fz electrode and music appreciation and clinical factors were
explored with Pearson’s product moment correlations. Statistical
inferences were derived for the following expected relational
directions: higher individual MMN amplitude and faster individual
MMN latency for more rated enjoyment of music, hours of music
listening, and knowledge of music, higher rated quality of musical
sounds with the CI, younger age, fewer years of deafness prior to
the CI implantation, and more years of CI experience. Each of the
16 MMNs (four features at four magnitudes) were tested for each
individual CI users. The results were not corrected for multiple
comparisons and only regarded as non-conclusive inspiration for
future studies.
2.7.2. Music discrimination thresholds for individual experienced CI
users
To further substantiate the main hypothesis on the relationship
between individual MMN and behavioral discrimination, we veri-
fied that the individual music discrimination threshold was passed
when the deviant magnitudes decreased. For all features, logistic
regression was applied to test whether the percentage of individu-
als showing individual MMN decreased as expected when the devi-
ant magnitude decreased. A significant result indicated that the
deviant magnitude crossed from above to below the individual’s
discrimination threshold.
Additionally, we attempted to replicate the common group-
level findings of similar intensity, timbre, and rhythm, but not
pitch discrimination, between individual CI users and normally
hearing. The percentage individuals showing MMN at each deviant
magnitude was compared between the CI and normally hearing
groups. Since the expected cell count tended to be less than 5 in
the contingency tables, the Fisher’s exact test was applied for the
group comparisons instead of the Pearson’s chi-squared test. Bon-
ferroni correction at p =.05/4 = 0.0125 was applied to interpret the
significance of the planned group comparisons with tests on each
of the four deviant magnitudes.
2.7.3. SCA statistics compared with preceding state-of-the-art
Finally, it was assessed whether SCA statistics showed higher
diagnostic accuracy compared to the preceding state-of-the-art.
For signal-to-interference-and-noise ratios (SNIRs) in the range of
approximately 1–10, the SCA method is known to show higher
gains in accuracy at lower SNIRs (Haumann et al., 2020). Therefore,
for each individual MMN test, a SNIR measure was estimated based
on the highest valued t-statistic from the t-tests applied in the SCA
statistics procedure. This SNIR estimate is a unitless quantity
reflecting the mean amplitude divided by the standard error of
the mean amplitude across trials. With the Welch’ test it was
investigated whether the SNIR was lower in the CI users compared
to the NH. For the CI and NH groups, by applying the Wilcoxon test
on the ROC areas under the curves it was tested whether the diag-
nostic accuracy was higher with the proposed SCA statistics
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Clinical Neurophysiology 148 (2023) 76–92
method compared to the state-of-the-art ‘‘t-cluster” method
(Bishop and Hardiman, 2010).
3. Results
3.1. MMN as a marker of auditory discrimination thresholds in
individual cochlear implant users
The behavioral discrimination thresholds were predicted with
high accuracy by the individual MMN detections, and the discrim-
ination thresholds estimated with the pre-attentive individual
MMN and attentive behavioral tests were similar (Fig. 2). Occa-
sional differences between the individual MMN and behavioral
results did not indicate functional differences and were mainly
explainable by measurement errors (Fig. 2B-C). For the adult expe-
rienced cochlear implant (CI) users and normally hearing (NH) con-
trols the occasional measurements errors were similar between
the individual MMN and the behavioral tests. This suggests that
the individual MMN is an accurate marker of auditory discrimina-
tion thresholds.
3.1.1. Diagnostic accuracy
The individual CI users’ ability (or inability) to discriminate
between the tones was predicted with high accuracy by the statis-
tically significant (or nonsignificant) individual MMN. The ROC
analysis showed that the automatic individual MMN detection is
a highly accurate marker of individual CI users’ auditory discrimi-
nation ability (Fig. 2A), AUC = 0.96 (95 % CI: [0.94, 0.98]), and is sig-
nificantly more accurate than the 50 % chance level (AUC = 0.50),
p <.001. Based on the ROC analysis, we recommend applying a the-
oretically expected confidence level of 99 % for the sensitivity (see
the Appendix D, Figure D1), which for the CI users resulted in an
empirical observed test sensitivity of 93.2 % (164/176), specificity
of 85.3 % (116/136), and balanced accuracy (BAC) of 89.2 %. This
individual MMN detection threshold p <.01 is applied for all subse-
quent results. Similar findings were observed for the NH controls:
AUC = 0.95 (95 % CI: [0.93, 0.97]), the comparison to chance level
shows a significant difference, p <.001, and the empirical test sen-
sitivity was 91.1 % (204/224), specificity 90.0 % (180/200), and BAC
90.5 %. In the following sections, results of supplementary assess-
ments are reported on the validity and precision of the individual
MMN-behavior relationship.
3.1.2. Validity
Relationships between MMN detection and behavioral detection:
When the behavioral test indicated ability to discriminate between
the tones compared to no discrimination ability, the group-average
MMN amplitude was significantly higher at the Fz electrode in the
CI users, Mdiff = –0.25 lV, 95 %CI: [–0.47, –0.03], t(84.6) = –2.3,
p =.026, d = –0.4, and the NH controls, Mdiff = –0.33 lV, 95 %CI:
[–0.61, –0.04], t(32.3) = –2.3, p =.026, d = –0.4 (Fig. 2B). When
the individual MMN was detected compared to interpreted as
absent, the group-average behavioral hit rate showed a tendency
of higher scores for the CI users, Mdiff=+11.2 %, 95 %CI: [–1.0,
23.4], t(38.5) = 1.9, p =.072, d = 0.4, and was significantly higher
for the NH controls, Mdiff=+18.4 %, 95 %CI:[6.5, 30.2], t(28.8) = 3.2,
p =.004, d = 0.8 (Fig. 2B). These results further substantiates that
the individual MMN is a valid marker of behavioral auditory
discrimination.
Similar MMN and behavioral discrimination thresholds: A relevant
question was whether the typical, occasional double dissociations
between the individual MMN and behavioral test outcomes
(Fig. 2B) were caused by functional differences in the underlying
auditory discrimination ability. When comparing the total number
of discrimination detections achieved with the MMN to the behav-
N.T. Haumann, Bjørn Petersen, A.S. Friis Andersen et al. Clinical Neurophysiology 148 (2023) 76–92

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Table 2
Percentage individuals with MMN detected and behavioral discrimination. Percentage individual MMN detections in the CI user group and the normally hearing (NH) group is
shown for each deviant feature and deviant magnitude, indicated by statistically significant spike density component analysis (SCA) components within the ROI at p <.01 (with
Benjamini-Yekutieli False Discovery Rate correction for multiple SCA component testing). ns. means no significant SCA components within the region of interest. Also is shown the
percentage individuals with behavioral discrimination, based on individual scores above chance level (>33 % correct).

Deviant feature Deviant magnitude Individual CI users Individual NH controls

MMN detected Behavioral discrimination MMN detected Behavioral discrimination
Intensity XL 100 % 64 % 100 % 100 %
L 82 % 64 % 86 % 79 %
M 73 % 27 % 71 % 71 %
S 64 % 27 % 50 % 43 %
Pitch XL 91 % 73 % 100 % 100 %
L 100 % 91 % 93 % 100 %
M 73 % 82 % 86 % 100 %
S 55 % 73 % 100 % 100 %
Timbre XL 100 % 100 % 93 % 100 %
L 82 % 100 % 86 % 100 %
M 55 % 82 % 86 % 91 %
S 91 % 91 % 86 % 79 %
Rhythm XL 91 % 100 % 100 % 100 %
L 100 % 91 % 100 % 100 %
M 91 % 100 % 93 % 100 %
S 100 % 73 % 93 % 64 %

ioral tests (Table 2) for each group, deviant feature, and deviant r = 0.31, which suggests that the MMN and behavioral tests were
magnitude, no significant differences were found between the similarly precise.
MMN and behavioral tests (Appendix D, Table D2). These results
suggest that the individual MMN and behavioral tests reflect sim- 3.1.4. Exploratory correlations with music appreciation and clinical
ilar auditory discrimination thresholds. factors
No relationship between MMN latency and behavioral detection: With regards to music appreciation, CI users providing higher
When the behavioral test showed ability to discriminate between ratings of enjoyment of listening to music tended to show faster
the tones compared to no discrimination ability, the group- individual MMN latency for the S (1-semitone) pitch deviant (scat-
average MMN peak latency did not differ significantly for the CI ter plots are shown in Appendix D, Figure D2), r(6) = –0.91, p =.011.
users, Mdiff = –11 ms, 95 %CI: [–30, 8], t(44.4)=, p =.239, d = –0.3, Also, CI users providing higher ratings of sound quality tended to
and only showed a weak tendency for the NH controls in the oppo- show higher individual MMN amplitudes (i.e., more negativity at
site than expected (slowing instead of speeding up) direction, Fz) for the S (bright piano), r(11) = –0.77, p =.006, and the XL (gui-
Mdiff=+23 ms, 95 %CI: [1, 46], t(21.2) = 2.2, p =.043, d = 0.6. tar), r(11) = –0.69, p =.019, timbre deviants (Appendix D,
Figure D2).
With respect to clinical factors, fewer years of deafness prior the
3.1.3. Precision CI implantation tended to be related to higher individual MMN
Behavioral detections were occasionally missing when individ- amplitude, r(11) = 0.68, p =.020, and faster individual MMN
ual MMN was detected above the ‘‘false MMN” detection rate latency, r(11) = 0.65, p =.031, for the L rhythm deviant (Appendix
(Fig. 2B). Vice versa, occasionally (on average 14.7 % (20/136) cases D, Figure D3).
for CI users and 10.0 % (20/200) cases for NH controls), individual No additional significant correlations were observed between
MMN was missing when behavioral discrimination was detected individual MMN amplitude or latency and music appreciation
above chance level (Fig. 2B). As expected from the measurement and clinical factors. The p-values concerning music appreciation
error hypothesis, lower deviant magnitudes were significantly and clinical factors were not corrected for multiple comparisons,
related to a higher percentage of missing behavioral or MMN and the observed significant tendencies should be interpreted with
detections (Fig. 2C) in both CI users, model v2(1) = 9.8, p =.002, caution.
R2N = 0.08, exp(b) = 1.6, 95 %CI: [1.2, 2.2], p =.002, and NH controls,
model v2(1) = 16.9, p <.001, R2N = 0.12, exp(b) = 2.0, 95 %CI: [1.4, 3.2. Music discrimination thresholds for individual experienced CI
2.9], p <.001.The highest number of missing discrimination ability users
detections occurred at the S (small) deviant magnitude in both CI
users and NH (Fig. 2C) (for further details, see Appendix D, For the experienced CI users, the tested intensity and pitch devi-
Table D1). The deviant magnitudes where detections were gener- ant magnitudes were crossing 50 %-64 % of the participants’ dis-
ally missing were not significantly different between MMN and crimination thresholds, whereas the tested small timbre and
behavioral tests (Fig. 2C) for the CI users, U = 348.0, n = 52, rhythm deviants remained above most (91 %-100 %) of the experi-
p =.580, r = 0.08, and the NH controls, U = 124.5, n = 39, p =.065, enced CI participants’ discrimination thresholds (Table 2). As
3
Fig. 2. MMN as a marker of auditory discrimination thresholds in individual cochlear implant users. Results are shown for cochlear implant (CI) users and normally
hearing (NH). (A: Diagnostic accuracy) The ROC curves show the sensitivity (% correct individual MMN-based automatic diagnosis of ‘‘discrimination inability” for the
repeated tones) and specificity (% correct individual MMN-based automatic diagnosis of ‘‘discrimination ability” when attentive discrimination was above chance level)
across varied p-thresholds. The diagonal line indicates the 50 % chance level, and the shaded error areas the 95 % bias-corrected and accelerated bootstrap confidence
intervals. (B: Validity) Relationships between peak MMN amplitude in lV at the Fz electrode (measured within the region of interest) and attentive hit rate in %. The
horizontal dashed line marks the 33 % chance level for the attentive behavioral test. Error bars indicate the 95 % confidence intervals, and individual cases are marked by grey
circles. (C: Precision) Comparisons between the % observations with missing attentive detections when MMN is detected and missing MMN detections when attentive
discrimination is detected. Error bars indicate the 95 % confidence intervals, and individual cases are marked by grey circles. Significance levels: *** p <.001, ** p <.01, * p <.05, y
p <.10.

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expected, the experienced CI users showed similar music discrim-
ination thresholds compared to NH controls, except for the pitch
discrimination thresholds that were higher for the experienced CI
users in comparison to the NH (Table 2).
3.2.1. Intensity
All experienced CI users showed significant individual MMN
responses to the extra-large (XL) intensity deviant (Table 2). Low-
ering the intensity deviant magnitude resulted in a significant
decay in the percentage individual CI users showing MMN, model
v2(1) = 5.0, p =.025, R2N = 0.17, exp(b) = 0.44, 95 %CI: [0.20, 0.97],
p =.042.
Similar findings were observed for the NH control group
(Table 2). All NH showed individual MMN to the XL intensity devi-
ant. Lowering the intensity deviant magnitude resulted in a signif-
icant decay in the percentage individual NH with MMN detected,
model v2(1) = 11.7, p <.001, R2N = 0.29, exp(b) = 0.32, 95 %CI:
[0.15, 0.69], p =.004.
Comparisons between the experienced CI and NH groups
showed that the percentage individual MMN detection was the
same for the XL intensity deviant and not significantly different
at the large (L), medium (M), and small (S) deviant magnitudes
(Table 3) (Bonferroni corrected significance level for the four
planned comparisons: p =.05/4 = 0.0125). This means that experi-
enced CI users and NH controls have similar intensity discrimina-
tion thresholds according to the individual MMN results. The
individual MMN results were consistent with the behavioral test
results (Appendix E, Table E1).
3.2.2. Pitch
Among the experienced CI users, 91 % showed significant indi-
vidual MMN responses to the XL pitch deviant (Table 2). Lowering
the pitch deviant magnitude resulted in a significant decay in the
percentage individual CI users with MMN detected, model
v2(1) = 6.8, p =.009, R2N = 0.23, exp(b) = 0.37, 95 %CI: [0.16, 0.87],
p =.022.
All NH showed individual MMN to the XL intensity deviant
(Table 2). Lowering the pitch deviant magnitude did not result in
a significant decay in the percentage individual NH with MMN
detected, model v2(1) = 0.1, p =.790, R2N = 0.00, exp(b) = 0.87,
95 %CI: [0.30, 2.48], p =.791.
Comparisons between the experienced CI and NH control
groups showed that the percentage of individual MMN detection
was not significantly different at the XL, L, and M deviant magni-
tudes, though, at the S deviant magnitude, significantly fewer CI
users (55 %) than NH controls (100 %) showed individual MMN
(Table 3) (Bonferroni corrected significance level for the four
planned comparisons: p =.05/4 = 0.0125). This means that, accord-
ing to the individual MMN results, the experienced CI users’ pitch
discrimination thresholds were often between 1–2 semitones for
pitch decrease (between 6 % and 11 % decrease in Hz), whereas
determining the discrimination thresholds for the NH required
smaller intervals than the smallest tested 1 semitone pitch
decrease. The behavioral discrimination test showed similar ten-
dencies, which, however, did not reach statistical significance
(Appendix E, Table E1).
3.2.3. Timbre
All experienced CI users showed significant individual MMN
responses to the XL timbre deviant (Table 2). Lowering the timbre
deviant magnitude did not result in a significant decay in the per-
centage of individual CI users with MMN detection, model
v2(1) = 1.1, p =.291, R2N = 0.04, exp(b) = 0.69, 95 %CI: [0.34, 1.40],
p =.302.
Among the NH controls, 93 % showed individual MMN to the XL
timbre deviant (Table 2). Lowering the timbre deviant magnitude
did not result in a significant decay in the percentage of individual
NH with MMN detection, model v2(1) = 0.3, p =.587, R2N = 0.01, exp
(b) = 0.82, 95 %CI: [0.40, 1.68], p =.589.
Comparisons between the experienced CI and NH control
groups showed that the percentage of individual MMN detection
was not significantly different at the XL, L, M, and S deviant mag-
nitudes (Table 3) (Bonferroni corrected significance level for the
four planned comparisons: p =.05/4 = 0.0125). The individual
MMN results were consistent with the behavioral test results
(Appendix E, Table E1).
3.2.4. Rhythm
Among the experienced CI users, 91 % showed significant indi-
vidual MMN responses to the XL rhythm deviant (Table 2). Lower-
ing the rhythm deviant magnitude did not result in a significant
decay in the percentage individual CI users showing MMN, model
v2(1) = 0.4, p =.512, R2N = 0.03, exp(b) = 1.55, 95 %CI: [0.40, 6.09],
p =.528.
Similar findings were observed for the NH control group
(Table 2). All NH showed MMN to the XL rhythm deviant. Lowering
the rhythm deviant magnitude did not result in a significant decay
in the percentage individual NH showing MMN, model v2(1) = 1.9,
p =.173, R2N = 0.12, exp(b) = 0.35, 95 %CI: [0.6, 2.2], p =.256.
Comparisons between the experienced CI and NH control
groups showed that the percentage of individual MMN detection
was not significantly different at the XL, the same at the L deviant,

Table 3
Comparisons between the percentage of cochlear implant and normally hearing individual MMN detections. Showing the Pearson’s chi-squared test results. The p-values are
corrected with Fisher’s exact test. ** indicates statistically significant difference between the cochlear implant and normally hearing groups at p <.01.

Feature Magnitude n df v2 p u
Intensity XL 25 1 0.0 1.000 0.00
L 25 1 0.1 1.000 0.05
M 25 1 0.0 1.000 0.01
S 25 1 0.5 0.689 0.14
Pitch XL 25 1 1.3 0.440 0.23
L 25 1 0.8 1.000 0.18
M 25 1 0.6 0.623 0.16
S 25 1 8.0 0.009** 0.56**
Timbre XL 25 1 0.8 1.000 0.18
L 25 1 0.1 1.000 0.05
M 25 1 3.0 0.177 0.35
S 25 1 0.2 1.000 0.08
Rhythm XL 25 1 1.3 0.440 0.23
L 25 1 0.0 1.000 0.00
M 25 1 0.0 1.000 0.03
S 25 1 0.8 1.000 0.18

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Fig. 3. Grand-average difference waveforms with spike density component analysis (SCA) statistics. Difference waveforms shown for the cochlear implant (CI) users and
normally hearing (NH) groups for each deviant feature and magnitude. Vertical axes indicate voltage in lV, horizontal axes peristimulus time in milliseconds. Shaded colors
indicate group-level bootstrap 95 % confidence intervals, and thin lines depict the individual-level waveforms of significant SCA component(s) (projected and mixed onto the
EEG channels). Group-average topographies at the peak latency (measured within the region of interest) are shown above the waveforms; cold colors indicate negative and
warm colors positive voltages between –4 to + 4 lV. * (p <.05) and ** (p <.01) indicate that MMN was detected in significantly fewer individuals when the deviant magnitude
was lowered.

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N.T. Haumann, Bjørn Petersen, A.S. Friis Andersen et al.
and not significantly different at the M and S deviant magnitudes
(Table 3) (Bonferroni corrected significance level for the four
planned comparisons: p =.05/4 = 0.0125). The individual MMN
results were consistent with the behavioral test results (Appendix
E, Table E1).
3.3. SCA statistics compared with preceding state-of-the-art
The proposed SCA statistics was more accurate than the preced-
ing state-of-the-art. The initial individual MMN signal-to-noise-
and-interference ratio (SNIR) was significantly lower in the CI users
(average peak SNIR = 4.3) than in the NH controls (average peak
SNIR = 5.0), Mdiff = –0.7, 95 %CI: [–1.2, –0.3], t(253.9) = –3.1,
p =.002, d = –0.4. As expected, for the CI users with relatively low
SNIR, the SCA statistics led to significantly higher diagnostic accu-
racy (balanced accuracy (BAC) = 89.2 %) in comparison to the state-
of-the-art ‘‘t-cluster” method (BAC = 86.1 %) (Fig. 2A), area under
the curve difference (AUCdiff) = 0.02 (95 % CI: [0.01, 0.03]),
p <.001, d = 0.3. Also, as expected for the already high SNIRs of
the NH controls, the proposed SCA statistics showed similarly high
accuracy (BAC = 90.5 %) in comparison to the ‘‘t-cluster” method
(BAC = 91.0 %), AUCdiff = –0.00 (95 % CI: [–0.01, 0.00]), p =.466,
d = –0.0.
Furthermore, the SCA components succeeded in modeling med-
ian 99.87 % (range: 70.75 %-99.98 %) of the variance in the CI users’
individual EEG waveforms. Similarly, the SCA components mod-
eled median 99.86 % (range: 85.09 %-99.99 %) of the variance in
the NH controls’ individual EEG waveforms. This shows that the
modeling performance of the SCA method was similarly high for
individual CI users and NH. (More details on individual-level and
group-level MMN topographies and waveforms before and after
applying SCA statistics are available in Fig. 3 and Appendix E, Fig-
ure E1, Figure E2, Figure E3, Figure E4, Figure E5, and Figure E6.)
4. Discussion
In this study, we investigated whether the statistical detection
of individual MMN responses is an accurate neurobiological mar-
ker of behavioral individual music discrimination thresholds of
cochlear implant (CI) users. Automatic MMN detections for indi-
vidual CI users showed a high diagnostic balanced accuracy
(BAC) of 89.2 % and a similarly high BAC of 90.5 % for normally
hearing (NH) controls. For each deviant magnitude and feature,
the number of participants showing no MMN detection and no
behavioral discrimination above chance level did not differ signif-
icantly within the CI and the NH groups, suggesting that the sound
discrimination thresholds estimated with the individual MMN and
the behavioral tests were similar. Also, there was lower congru-
ency between the MMN and behavioral test results for smaller
deviant magnitudes. Though, for each deviant magnitude, auditory
feature, and participant group, there were no significant differ-
ences between the number of participants with missing MMN
(when behavioral discrimination was detected) compared to the
number of participants with missing behavioral discrimination
(when MMN was detected), suggesting that the MMN and behav-
ioral tests were equally precise for estimating the individual sound
discrimination thresholds. These findings are particularly promis-
ing, e.g., for applying the individual MMN to test the development
of individual pediatric CI users, who can complete MMN tests
(Torppa et al., 2018, Torppa et al., 2014, Torppa et al., 2012) but
commonly experience difficulties with completing behavioral tests
(e.g., Kuki et al., 2013, Kumari et al., 2016). All these findings were
partly achieved with an optimized, semi-automatic, and easy to
inspect (by suppressing interfering cortical signals from the EEG
images) spike density component analysis (SCA) statistics method,
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Clinical Neurophysiology 148 (2023) 76–92
which showed higher diagnostic accuracy (BAC = 89.2 %) compared
to the preceding state-of-the-art on individual-level EEG statistics
methods (BAC = 70.8 %-85.3 %) (Bishop and Hardiman, 2010,
McGee et al., 1997).
Altogether, the improved accuracy in measuring individual
MMN responses opens new avenues for testing the progress of
the individual CI user with rehabilitation interventions, such as
the effects of music training even suggesting improved speech pro-
cessing in pediatric CI users related to music training (Petersen
et al., 2015, Torppa et al., 2018).
4.1. MMN as a marker of auditory discrimination thresholds in
individual cochlear implant users
4.1.1. Functional relationship between MMN and behavioral
discrimination thresholds
The behavioral testing of sound discrimination is based on
slower attentive responses compared to the individual MMN, and
contextual information for sounds both preceding and succeeding
the deviant sound can influence the behavioral response. By con-
trast, the individual MMN response is a faster, automatic, preatten-
tive, neural response compared to the behavioral response, and the
individual MMN follows immediately after the onset of the deviant
sound (Näätänen et al., 2017). Despite these differences in process-
ing stages, the present results did not suggest functional differ-
ences between the individual MMN detection and the behavioral
discrimination. While evidence for a correspondence between the
MMN and behavioral auditory discrimination exists for groups of
CI listeners (e.g., Rahne et al., 2014), we are not aware of previous
studies showing a direct relationship between MMN and behav-
ioral sound discrimination ability at the individual level in both
normally hearing listeners and CI users. Moreover, the individual
discrimination thresholds were similar, regardless of whether they
were estimated with the MMN or a behavioral test. These findings
mutually support that the individual MMN is an accurate marker of
auditory discrimination thresholds in individual CI users. The find-
ings also suggest that incongruent MMN and behavioral outcomes
are not always explainable by functional differences, also, mea-
surement errors near the discrimination thresholds and
suprathreshold ceiling effects on the behavioral hit rates should
be taken into consideration.
4.1.2. The influence of measurement errors on MMN and behavioral
tests
We observed that the individual MMN and behavioral test
results were more disturbed by measurement errors at the smaller
deviant magnitudes near the discrimination thresholds compared
to the larger deviant magnitudes well above the discrimination
thresholds. For the here tested adult CI user and NH groups we
found that the measurement errors were similar, regardless of
whether the MMN or the behavioral tests were applied. Though,
the sources of the measurement errors are known to differ
between the MMN and the behavioral test. While the individual
MMN is mainly masked by neural interferences from ongoing
background brain processes (e.g., Haumann et al., 2020), the
behavioral test is typically confounded by attentive, cognitive, or
motoric disabilities (e.g., Norrix, 2015). Infants and children are
known to elicit measurable MMN responses to deviant sounds
(Fellman and Huotilainen, 2006, Torppa et al., 2012), whereas mea-
surement errors seem to be more limiting behavioral testing of
infants and children (Kuki et al., 2013, Norrix, 2015) compared
to, e.g., the adult groups in the present study. A study found that
behavioral observation audiometry testing for infants reached a
sensitivity of 94.2 % but only a specificity of 67.7 % (with auditory
brainstem response applied as the correct reference test). This
means that approximately every third infant was incorrectly diag-
N.T. Haumann, Bjørn Petersen, A.S. Friis Andersen et al.
nosed as having a hearing disorder, due to measurement errors in
the behavioral test (Kuki et al., 2013). One advantage of the indi-
vidual MMN is that it is measurable without requiring the atten-
tive, cognitive, or behavioral abilities needed for behavioral
testing (Näätänen et al., 2017). Thereby, the individual MMN could
potentially facilitate better auditory discrimination tests for CI
users with attentional, cognitive, or motor impairments. Moreover,
the individual MMN might be considered more ecologically valid
than behavioral testing, because the MMN indicates that sound
discrimination ability has been established at an auditory process-
ing level where attentive and cognitive effort is minimal, which is
an important aspect for diagnostics of hearing performance in real-
istic listening situations, in which minimization of required atten-
tion and cognitive effort is desirable (Faulkner and Pisoni, 2013,
Perreau et al., 2017). Another potential advantage might be a pos-
sibly higher sensitivity of the individual MMN to listening effort
than behavioral measures. For instance, if the fast early-stage
MMN is missing for a deviant stimulus, suggesting that the audi-
tory discrimination has not been established pre-attentively,
behavioral discrimination might still be detected based on slower
later-stage auditory processes requiring more listening effort.
4.1.3. Suprathreshold ceiling effects on behavioral hit rates but not on
MMN amplitudes
In the present study we investigated binary diagnostic out-
comes, where the individual MMN was either detected or not,
and we found that the individual MMN detection was significantly
related to sound discrimination being present or not. An outstand-
ing question is whether CI users perceive larger deviant magni-
tudes as larger compared to smaller deviant magnitudes, and
whether these perceptual magnitude differences might be
reflected by the individual MMN amplitudes. For this purpose,
the traditional application of behavioral hit rate measures in
MMN studies (Bishop and Hardiman, 2010, Petersen et al., 2015,
Ponton et al., 2000, Rahne et al., 2014, Sandmann et al., 2010,
Timm et al., 2014, Torppa et al., 2018) might maintain a validity
issue, because the hit rate indicates the probability of perceiving
a difference, and it has a noticeable ceiling effect for suprathresh-
old stimuli (due to the ‘‘S”-shaped relationship between the devi-
ant magnitude and the discrimination probability) (Grondin,
2016). By contrast, the MMN amplitude increases continuously
for deviant magnitudes above the discrimination threshold
(Näätänen et al., 2017). In a group-level analysis on the same data-
set analysed in the present study (Petersen et al., 2020),
suprathreshold ceiling effects were evident in behavioral hit rates,
whereas the MMN amplitudes continued increasing for deviant
magnitudes above the discrimination threshold (especially for
the NH pitch, timbre, and rhythm results). Also, the suprathreshold
ceiling effect appears to be present in the individual-level results
(compare Fig. 3 to Appendix Table D1). In future studies, a behav-
ioral measure of perceptual magnitude, e.g., a Likert or visual ana-
logue scale, might be more comparable to the MMN amplitudes
than hit rates. As such, the individual MMN amplitude might be
applied as a more linear objective estimate of perceived magnitude
of sound differences compared to behavioral hit rates.
4.1.4. Exploratory correlations with music appreciation and clinical
factors
The rated enjoyment of music and quality of life of CI users have
been found to be related to the rated sound quality achieved with
the CI (Dritsakis et al., 2017, Fuller et al., 2022, Lassaletta et al.,
2007). Our exploratory findings at the neural level suggested that
CI users with higher ratings of enjoyment of listening to music
might be predicted by faster individual MMN latencies for the 1-
semitone pitch deviant. This is in line with previous findings that
moods or emotions in music are often conveyed by 1-semitone dif-
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Clinical Neurophysiology 148 (2023) 76–92
ferences, and inefficient auditory processing of the 1-semitone dif-
ferences limits CI users ability to perceive musical moods or
emotions, which are part of the enjoyment of music listening
(Caldwell et al., 2015). Moreover, we observed that individual CI
users with higher MMN amplitude for the bright piano and guitar
timbre deviants might predict higher ratings of the perceived qual-
ity of musical sounds. Furthermore, our findings suggested that
earlier CI implantation after the severe hearing loss might lead to
higher individual MMN amplitude and faster individual MMN
latency for the large –103 ms rhythm deviant (that occurs maxi-
mally out of phase in between the 205 ms tone stimulus onset
asynchrony and shows the average highest rhythm MMN ampli-
tude in the experienced CI users (Petersen et al., 2020)). It should
be mentioned that these relationships were not observed in previ-
ous group analysis on the same EEG data when the new SCA statis-
tics method was not applied (Petersen et al., 2020). The
replicability of these uncorrected exploratory relationships
between individual MMN and music appreciation and clinical fac-
tors would need to be further tested in future studies before any
conclusions can be drawn.
4.2. Music discrimination thresholds for individual experienced
cochlear implant users
For the first time, we estimated music discrimination thresh-
olds for experienced individual cochlear implant (CI) users based
on individual MMN detections.
4.2.1. Intensity
As expected, MMN was detected in fewer individual CI users
and normally hearing (NH) participants when the intensity deviant
magnitudes were smaller, which supports the validity of the indi-
vidual MMN as a marker of music discrimination thresholds. The
neural discrimination thresholds for the intensity differences were
similar between the individual experienced CI users and the NH
controls. This suggests that, despite the dynamical range is limited
with CI (Petersen et al., 2020), the individual experienced CI users
detected the dynamical changes between –3 to –12 dB in the music
stimuli equally well compared to the NH controls.
4.2.2. Pitch
For the pitch differences, also, MMN was detected in fewer indi-
vidual CI users when the deviant magnitudes were smaller, which
again supports the validity of the individual MMN as a marker of
music discrimination thresholds in individual CI users. The individ-
ual CI users showed neural ability to detect the XL, L, and M pitch
deviants comparable to the NH. However, only 55 % (6/11) of the
experienced CI users showed individual significant MMN for the
small pitch deviant of 1 semitone decrease (-6% in Hz), whereas
significant individual MMN was detected in all (14/14) NH for this
small pitch deviant. This is in line with previous research showing
that pitch perception with CI is limited and varied across individu-
als compared to NH (Jiam et al., 2019, Oxenham, 2008), and this
finding further supports the validity of the individual MMN as a
marker of music discrimination thresholds in CI listening.
4.2.3. Timbre
For the timbre feature, all individual experienced CI users and
NH showed comparable ability to detect the differences in tone
color, or sound quality. These findings are more promising than a
recent behavioral study showing overall lower music instrument
timbre discrimination in experienced CI users than NH (Jiam
et al., 2019), which might, though, be partly explained by the rela-
tive simplicity in detecting whether the sound differed in timbre
(compared to the more complex task of identifying the correct
N.T. Haumann, Bjørn Petersen, A.S. Friis Andersen et al.
image of a playing instrument among 16 possible music
instruments).
4.2.4. Rhythm
For the rhythm feature, most experienced CI users (93 %, 10/11)
showed significant individual MMN for even the smallest 26 ms
rhythm deviant, which was comparable to the NH individual
MMN detections (100 %, 14/14). This is consistent with previous
findings suggesting that perception of relatively simple rhythmical
structure is comparable between CI and NH (Innes-Brown et al.,
2013, Jiam and Limb, 2019).
4.3. Limitations
4.3.1. Clinical feasibility
The musical stimuli of the CI MuMuFe paradigm might be con-
sidered relatively complex for clinical settings. Though, first, the
MMN paradigm applies a task-free, passive listening procedure
that is less challenging, even for paediatric patients (Torppa
et al., 2018, Torppa et al., 2014, Torppa et al., 2012), compared to
auditory judgment tests and questionnaires (e.g., Kuki et al.,
2013, Kumari et al., 2016). Also, faster few-minutes shortened ver-
sions of the full paradigm could be adopted, e.g., by testing only
particularly challenging deviants for an individual CI user, such
as pitch deviants of specific magnitudes. Second, a majority
(90 %) of CI users report they are interested in improving their
music perception skills (Gfeller et al., 2019), suggesting that music
is a particularly engaging type of stimulus for testing auditory per-
ception, and objective tests are required to trace the development
of the music perception skills. Third, cross-over relationships
between music and language perception abilities have been
reported (for reviews, see Besson et al., 2018, Jancke, 2012, Kraus
and Slater, 2015, Patel, 2003, Torppa and Huotilainen, 2019), sug-
gesting that the testing of music perception abilities can indicate
more general traits of auditory perception shared with language
perception. Fourth, the application of more complex but naturalis-
tic stimuli has the benefit of increasing the ecological validity in
the testing of the CI users’ auditory perception of complex sounds,
which can be more challenging than the perception of simpler
sounds (Jiam and Limb, 2020). A fifth point is that music stimuli
are by nature often repetitive (Huron, 2013), and repetitiveness
is a wanted prerequisite for the measurement of mismatch-
negativity (MMN) responses to auditory deviants (Näätänen
et al., 2017).
Moreover, there are ongoing improvements in EEG recording
with CI users, e.g., a recent feasibility study showed that cortical
auditory evoked responses (CAEPs) can be recorded directly with
electrodes built into the receiver and the cochlear array on the con-
tralateral CI device to the ear of stimulation (resulting in CAEP sig-
nals of comparable quality to conventional scalp recordings with
Fz and mastoid electrodes), thus making it unnecessary to prepare
electrodes located on the scalp prior to the measurements (Attias
et al., 2022).
Finally, developments are currently being made towards auto-
matic suppression of CI artifacts in clinical EEG data (for a review,
see Intartaglia et al., 2022). Despite the complexity of the
individual-level statistics, the individual MMN can already be
detected automatically as shown here and elsewhere (Bishop and
Hardiman, 2010, McGee et al., 1997).
4.3.2. Auditory diagnostics and screening
The results did not approach 100 % (>99 %) sensitivity, which
suggests that the individual MMN is not recommendable for
large-scale universal screening for general auditory deficits.
Though, the approximately 90 % accuracy of the individual MMN
is high and desirable for diagnostics on music discrimination abil-
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Clinical Neurophysiology 148 (2023) 76–92
ity. We recommend that the automatic statistical diagnostics is fol-
lowed up by visual confirmation. Since the amplitude range of
spurious ‘‘false MMN” detections was relatively low, tests resulting
in low individual MMN amplitudes might be followed up by
retesting.
4.3.3. N1 or MMN?
Subtracting the average standard response will include the dif-
ference in N1 between the deviant and standard responses. This
ensures that the N1 will not directly be present in the difference
wave, assuming the N1 does not differ between the standard and
deviation tones. However, if there is a disinhibition of the N1 at
the deviant tones, this would result in an N1 disinhibition
response, which some considers also to be a subcomponent of
the MMN (Gu et al., 2018, May and Tiitinen, 2004). Regardless of
these theoretical distinctions, the present findings suggested that
in practice these early latency negative fronto-central evoked
responses could accurately predict behavioral music discrimina-
tion ability.
4.3.4. Opposite diagnostical and statistical terminology for CAEP tests
In this study, and all other studies on cortical auditory evoked
potential tests of sound detection and discrimination ability, there
is an opposition between the diagnostical and statistical definitions
of ‘‘sensitivity” and ‘‘specificity”. To avoid contradiction with the
common clinical terminology, we think it makes most sense to
apply the diagnostical definition. Diagnostic ‘‘sensitivity” means
individual MMN absence or retaining the null-hypothesis, because
‘‘sensitivity” indicates the abnormality or disease detection, which
is the lack of discrimination indicated by the individual MMN
absence or retainment of the null-hypothesis. Diagnostic ‘‘speci-
ficity” means that individual MMN was present, or the rejection
of the null-hypothesis, which means the test was passed without
indication of abnormality. Since diagnostic ‘‘sensitivity” is more
important than ‘‘specificity”, it is important to keep the correct
diagnostic definition to avoid confusion from the clinical perspec-
tive. This is, nevertheless, the opposite of the common statistical
definition, where ‘‘sensitivity” would mean the null-hypothesis
was rejected or individual MMN detection, and ‘‘specificity” would
mean the null-hypothesis was retained or individual MMN
absence.
5. Conclusion
We investigated the feasibility of applying the individual MMN
as a marker of musical sound discrimination thresholds in individ-
ual cochlear implant (CI) users. We introduced an optimized spike
density component analysis (SCA) statistics method to improve the
accuracy of the individual MMN detections. Our findings showed
that the automatically detected individual MMN correctly pre-
dicted the sound discrimination ability for CI users and normally
hearing (NH) in approximately 9/10 cases. Moreover, the individ-
ual MMN findings suggested that adult CI users can reach similar
music discrimination abilities for intensity, timbre, and rhythm
features compared to NH after sustained CI experience (average
7 years). In conclusion, the individual MMN can be applied as an
accurate diagnostic marker for assessing music discrimination in
CI users, which is especially beneficial for individuals for whom
MMN measurements are feasible but behavioral testing is limited,
such as pediatric CI users.
Author contributions
NTH wrote the first manuscript draft, preprocessed the EEG
data, designed and programmed the SCA statistics method, and
N.T. Haumann, Bjørn Petersen, A.S. Friis Andersen et al.
conducted the individual- and group-level analyses. BP, EB, PV, and
contributed to the conception and design of the study. BP and AA
conceived the paradigm and the behavioral test and created the
stimuli. AA organized and carried out the recruitment and tests.
KFF contributed with participant recruitments and manuscript
revisions. PV contributed with funding and manuscript revisions.
All authors contributed to manuscript revisions and read and
approved the manuscript.
Funding
NTHs contributions to the project were partly funded by the
Oticon Medical, Denmark, and partly by the Danish National
Research Foundation’s Center for Music in the Brain (DNRF117).
Declaration of Competing Interest
The authors declare that they have no known competing finan-
cial interests or personal relationships that could have appeared
to influence the work reported in this paper.
Acknowledgments
The authors wish to thank all the participants for their unre-
stricted commitment. We wish to thank Oticon Medical, Denmark,
and the Danish National Research Foundation who funded this
research. The authors thank MD Hanne Owen and CI coordinator
Minna Sandahl from the Clinic of Audiology at Aarhus University
Hospital and the Danish CI organization for assistance with recruit-
ment. Special thanks to Dora Grauballe, Center for Functionally
Integrative Neuroscience, for invaluable and unconditioned help
with bookings and management of laboratory facilities and to
research assistants Alberte Seeberg and Monica Ipsen for perfectly
managing participant communication and data collection. Also, we
thank Franck Michel for the important spare processer CI program-
ming, direct sound delivery to the CI via cable, and information
about the CI participants. A final thanks to Dr., MD, Therese Ovesen
for her great role in the initial phase of the project.
Appendix A. Supplementary material
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.clinph.2023.01.015.
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