Prenatal Music Exposure Induces Long-Term Neural Effects

Abstract

We investigated the neural correlates induced by prenatal exposure to melodies using brains' event-related potentials (ERPs). During the last trimester of pregnancy, the mothers in the learning group played the 'Twinkle twinkle little star' -melody 5 times per week. After birth and again at the age of 4 months, we played the infants a modified melody in which some of the notes were changed while ERPs to unchanged and changed notes were recorded. The ERPs were also recorded from a control group, who received no prenatal stimulation. Both at birth and at the age of 4 months, infants in the learning group had stronger ERPs to the unchanged notes than the control group. Furthermore, the ERP amplitudes to the changed and unchanged notes at birth were correlated with the amount of prenatal exposure. Our results show that extensive prenatal exposure to a melody induces neural representations that last for several months.

Full text

Prenatal Music Exposure Induces Long-Term Neural
Effects
Eino Partanen
1,2
*, Teija Kujala
1,3
, Mari Tervaniemi
1,2
, Minna Huotilainen
1,2,4
1Cognitive Brain Research Unit, Cognitive Science, Institute of Behavioral Sciences, University of Helsinki, Helsinki, Finland, 2Finnish Center of Excellence in
Interdisciplinary Music Research, Deparment of Music, University of Jyva
¨skyla
¨, Jyva
¨skyla
¨, Finland, 3Cicero Learning, University of Helsinki, Helsinki, Finland, 4Finnish
Institute of Occupational Health, Helsinki, Finland
Abstract
We investigated the neural correlates induced by prenatal exposure to melodies using brains’ event-related potentials
(ERPs). During the last trimester of pregnancy, the mothers in the learning group played the ‘Twinkle twinkle little star’ -
melody 5 times per week. After birth and again at the age of 4 months, we played the infants a modified melody in which
some of the notes were changed while ERPs to unchanged and changed notes were recorded. The ERPs were also recorded
from a control group, who received no prenatal stimulation. Both at birth and at the age of 4 months, infants in the learning
group had stronger ERPs to the unchanged notes than the control group. Furthermore, the ERP amplitudes to the changed
and unchanged notes at birth were correlated with the amount of prenatal exposure. Our results show that extensive
prenatal exposure to a melody induces neural representations that last for several months.
Citation: Partanen E, Kujala T, Tervaniemi M, Huotilainen M (2013) Prenatal Music Exposure Induces Long-Term Neural Effects. PLoS ONE 8(10): e78946.
doi:10.1371/journal.pone.0078946
Editor: Manuel S. Malmierca, University of Salamanca- Institute for Neuroscience of Castille and Leon and Medical School, Spain
Received May 20, 2013; Accepted September 17, 2013; Published October 30, 2013
Copyright: ß2013 Partanen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This study was financially supported by the Academy of Finland (grants 128840, 1135304, and 1135161; http://www.aka.fi/eng), ERANET-NEURON
(http://www.neuron-eranet.eu/) project Probing the Auditory Novelty System (PANS), the University of Helsinki (http://www.helsinki.fi/university/index.html)
graduate school grant and the Finnish Cultural Foundation (http://www.skr.fi/en). The funders had no role in study design, data collection and analysis, decision
to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: eino.partanen@helsinki.fi
Introduction
Rather than being born as ‘blank slate’, a newborn has
surprisingly extensive experiences on the surrounding world. In
particular, newborns seem to react to sounds during the fetal
period (see [1] for a review) and respond distinctly to them after
birth. For example, newborns seem to recognize familiar
environmental sounds [2] and melodies [3] from the prenatal
environment, discriminate between the native language of the
mother and other languages [4], and recognize mother’s voice [5]
from voices of other females. It was suggested that prenatal
learning facilitates, for example, language learning in infancy [6]
and provides a basis for attachment [5].
Fetal auditory learning becomes possible soon after the onset of
hearing, in humans by the 27 weeks gestational age (GA) [7], when
external auditory input starts to reorganize the auditory cortex [8].
Initially it was suggested that fetal auditory learning was limited to
the discrimination of low-pitch sounds features, such as the rhythm
of music and prosodic features of speech [9], as external high-
pitched sounds are attenuated in the utero [10]. However, fetuses
might perceive and recognize even the high-pitched sounds as
adult listeners can recognize speech sounds when attenuated
similarly as the external sounds in utero [11].
It is challenging to determine what sound features fetuses have
learned prior to birth (for a review, see [12]). While behavioral
measures (e.g., head-turning, non-nutritional sucking) are one
possible approach, brain’s event-related potentials (ERPs) can
provide more specific information on the neural correlates of the
types and features of sounds the fetuses can learn [13].
In adults, ERPs have been used to study both the effects of
passive exposure to sounds and active auditory learning. For
example, mere 15 minutes of passive exposure to sounds enhanced
P2 ERP response in adults [14]. Furthermore, active auditory
discrimination training enhanced P2 ERP responses and this
enhancement increased after each training session, lasting months
after the last auditory experience [15]. Also 1-year old infants
participating in active musical training had more positive ERP
responses to musical sounds than infants participating in passive
musical training [16]. While newborns and fetuses cannot actively
participate in learning, newborns were shown to learn during sleep
[17].
The prenatal auditory learning may also be seen as an
enhancement of Mismatch Negativity (MMN), a component of
ERPs widely been used in studies of learning and development
[18]. MMN represents the brain’s automatic change-detection
[18], reflects the formation of long-term memory representations
(for a review, see [18]), and is elicited even in the absence of
attention [19]. While in adults MMN is seen as a negative
deflection within 200–300 ms from change onset in the deviant-
minus-standard difference waveform, in infants MMNs of both
positive and negative polarity have been reported [20–25].
However, the deviant-minus-standard difference waveform may
also include other components, such as the positive P3a responses
associated with involuntary attention shifting in adults (e.g. [26]),
confounding the genuine MMN. In infancy, however, increased
attention towards the sounds has been shown to elicit an additional
negative component in addition to the positive MMN response in
the infant deviant-minus-standard waveform while the positive
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response remains unchanged [27,28]. Previous studies utilizing
MMN to investigate infant auditory discrimination have shown
that infants can neurally discriminate, for example, pitch changes
in melodies [25].
Previously, neuroscientific research has focused on the imme-
diate outcomes of fetal auditory learning after birth (for a review,
see [12]). To our knowledge, previous follow-up studies of fetal
learning have only shown cardiac effects for a melodic contour 6
weeks after birth [29]. Here we investigate with ERPs fetal
auditory learning of a familiar children’s’ melody (Twinkle twinkle
little star). Furthermore, we determine the persistency of the
learning effects by following up the infants for 4 months after birth.
We expected to see two possible effects due to prenatal exposure to
music: a general enhancement in the ERPs to the stimuli used in
the experiment, and specific learning effects seen as the elicitation
and enhancement of MMR response to changed sounds in the
melody.
Methods
Participants and ethics statement
12 Finnish- and bilingual Finnish and Swedish -speaking
women with non-complicated singleton pregnancies participated
in the learning group. In addition, a control group of 12 healthy
newborn infants of Finnish- and bilingual Swedish and Finnish -
speaking families were recruited after birth. Only one woman in
both learning and control groups was bilingual. Four months later, the
same infants, including the ones whose data were rejected from the
initial experiment, participated in a follow-up EEG experiment.
The mothers or both parents gave an informed oral consent for
their infants’ participation in the study. The parents received a
small monetary compensation for participating in the study, and
this signed transaction, using the parents’ tax deduction card, was
used to formally document the oral consent. In addition, the
contact details of the families were taken in writing, should any
need to contact the family again arise. The Ethical Committees of
the former Department of Psychology and the Helsinki University
Central Hospital approved both the study and the consent
procedure. After removing participants due to hardware issues
and excessive movement from both experiments, the final learning
group consisted of 10 infants in the initial experiment and 10 infants
at the follow-up experiment (11 and 8 infants, respectively, for the
control group).
At birth, the hearing of the infants in both groups was tested
with Evoked Oto-Acoustic Emissions (EOAE, ILO88 Dpi,
Otodynamics Ltd., Hatfield, UK). All infants passed the test and
were considered healthy by a neonatologist. The gestational age,
birth weight, APGAR score and the age at EEG experiment are
listed in Table 1. No statistically significant differences between
any background variables were found between the groups either at
birth or at the age of 4 months.
Prenatal stimulation
Mothers in the learning group played a learning CD at loud
volume at home (approximately 75 – 85 dB SPL) 5 times each
week from GA 29+0 (Gestational age; weeks+days) onwards until
birth and were told to destroy the CD after giving birth. The CD
contained 3 short excerpts of several musical melodies, alternating
with speech phrases (total duration of 15 minutes). Several
melodies and speech phrases were included on the CD to make
the listening more pleasant for the mother and also to capture the
attention of the fetus by changes in the auditory stimulation, which
might facilitate learning. One of the melodies was a 54-second
long melody of ‘‘Twinkle twinkle little star’’, played with a Roland
A-33 keyboard in G-major and the other musical sounds on the
CD were extremely different from both ‘‘Twinkle twinkle little
star’’ and each other, being either melodies from the study of
Tervaniemi et al. [30] or a classical piece by Sibelius. The mothers
in the learning group played the CD between 46 and 64 times (mean
57). The ‘‘Twinkle twinkle little star’’ –melody was repeated 3
times on the CD, and the fetuses heard the melody between 138 to
192 times (mean 171).
Stimuli and procedure
In the EEG-experiments a modified version of the ‘‘Twinkle
twinkle little star’’ -melody was played to the infants 9 times. In the
modified melody, 12.5% of the notes in the original melody were
replaced at random with B (H in German notation) -notes (called
changed sounds from now on; the unchanged notes are referred to as
unchanged sounds; see Figure 1). The changes are key-preserving as B
belongs to G-major scale and thus are not more salient than
unchanged notes on basis of the key of the melody. However, a
listener who is familiar with the original melody can recognize the
changed sounds easily (see, e.g., [31], for a similar paradigm). The
melody was played with a 600 ms stimulus onset asynchrony
(SOA) between the sounds. With the exception of the changed
sounds, all characteristics of the experimental melody (e.g. tempo,
key) were kept identical with the melody the infants were exposed
to prenatally. Speech phrases and other musical sounds, similar to
those on the learning tape, were presented between the melodies.
Table 1. Participant background information for the learning (L) and control (C)groups.
Gestational age (weeks
+
days) Birth weight (grams) APGAR score Age at EEG experiment (days)
Initial experiment L: 41+0(38+0242+0) C: 40+3
(37+5242+4)
L: 3834 (1975–4590) C: 3707
(3000–4700)
L: 9 (8–10) C: 9 (7–9) L: 16 (9–27) C: 13 (2–26)
Follow-up experiment L: 40+6(38+0242+0)
C: 40+0(37+5241+6)
L: 3703 (1975–4590) C: 3831
(3345–4700)
L: 9 (8–10) C: 8 (7–9) L: 144 (128–170) C: 133 (120–150)
Numbers denote means, the numbers in brackets denote minimum and maximum, respectively.
doi:10.1371/journal.pone.0078946.t001
Figure 1. An excerpt of the stimuli used in the experiment. The
image score above represents the original unchanged melody while the
score below shows the changed melody. Changed notes are marked
with asterisks.
doi:10.1371/journal.pone.0078946.g001
Fetal Music Learning
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During the newborn recordings, sounds were presented via
loudspeakers 20 cm to the left and to the right from the infant’s
head. In the four months follow-up recording the loudspeakers
were located one meter to the left and to the right of the infant due
to the infants being awake and possibly grabbing the loudspeakers
if they were placed too close to the infant. The sound intensity was
approximately 70 dB (SPL) at the infant’s head in both recordings.
ERP recording and data analysis
The newborn ERP recordings were conducted by trained nurses
at the Hospital for Children and Adolescents, Helsinki University
Central Hospital and the four-month follow-up recordings at the
Cognitive Brain Research Unit, University of Helsinki. Disposable
EEG electrodes were placed at F3, F4, C3, Cz, C4, P3, P4, T3,
and T4 scalp loci and the two mastoids according to the
international 10–20 system (T3 and T4 electrodes were omitted
from the four-month follow-up recording due to lack of signal in
the newborn recordings). EOG was monitored with electrodes
below and to the right of the right eye. EEG was recorded with a
sampling rate of 250 Hz through a band-pass filter of 0.1 to 40 Hz
using the NeuroScan recording system, referenced to the average
of the mastoid electrodes. During the recording the infants were
laying in a crib and the four-month-olds were either placed in an
infant car seat or in their parents’ or nurses’ lap.
The sleep stage of the infant was classified to be active (active
sleep, AS) when the EEG showed low-voltage high-frequency
activity, quiet (quiet sleep, QS) when it included either high-
voltage low frequency activity or trace alternants (high and low-
voltage slow waves alternating) and awake when the EOG
channels showed frequent and large eye movements or large
movement artefacts and on basis of the observations of a trained
nurse conducting the experiment (see, e.g., [32], for classification
criteria). The EEG data during which the infant was awake (even
for an occasional period of time), or with large artifacts, were
rejected during the visual analysis of the sleep stages
Offline, all the data were analyzed in sensor space. Initially the
data from newborns were first divided into sleep stages,
determined using the EEG, EOG, and the notes from the nurses.
AS is characterized by low-voltage high-frequency activity, QS by
either high-voltage low frequency activity or trace alternants (high
and low-voltage slow waves alternating), while during wakefulness
EOG channels show frequent and large eye movements or EEG
channels large movement artifacts [32]. The newborn wakefulness
was determined both on the basis of EEG and of the observations
of a trained nurse conducting the experiment. Because of extensive
artifacts, the data recorded during the infant’s wakefulness were
discarded from further analysis. The data collected during active
and quiet sleep were combined. The infants in the learning group
spent 0–100% (mean 64%) of their time in quiet sleep (27 – 100%,
mean 73%, for the control group), measured by the number of
accepted epochs in quiet sleep versus accepted epochs in active
and quiet sleep combined. By four months of age, the infants sleep
much less during the day than newborns do [33], and the four-
month old infants spent most of the experiment awake. Unlike
newborns, the four-month-olds did not move extensively during
the recording when awake, and thus these data were used as well,
after removing any data with movement artifacts.
During data analysis the two stimuli immediately following a
changed sound were discarded from the analysis. The data were
offline-filtered with a zero-phase band-pass filter (1 to 20 Hz) and
divided into epochs of 700 ms starting 100 ms prior to sound
onset. T3, T4, P3, and P4 electrodes were removed from further
analysis due to lack of signal. All epochs including movement
artifacts or those in which the amplitude on any of the channels
exceeded 6100 mV were excluded from further analysis. The
epochs for the unchanged and changed sounds were separately
averaged. To study MMRs, difference signals were formed by
subtracting the response to the unchanged sound from that to the
changed sound. Group-average signals were formed for un-
changed and changed sounds, and for difference signals, separately
for both learning and control groups. To improve the S/N ratio, the
signals from F3, F4, C3, Cz, and C4 electrodes were averaged
together.
ERP and MMR peak latencies were determined from the
group-average waveforms, separately for both groups and both
experiments. During the first year of life, unlike in adults, the most
salient component in the auditory ERP waveform is P350 response
[21,34]. To assess P350 for the newborns, the latency of the most
positive peak in the group-average waveforms between 100 and
600 ms was selected for analysis. In the four-month-olds, the
responses for the unchanged and the changed sounds between 100
and 600 ms showed two positive peaks, possibly corresponding to
P150 and P350 [21], both of which were analyzed further. In
newborns, the difference waveform showed a single positive
deflection while in four month olds the difference waveform
consisted of a low-amplitude negative deflection followed by a
positive peak (see also [35]), all of which were separately analyzed.
After determining the peak latencies, the mean ERP and MMR
amplitudes were calculated as a mean voltage in a 60-ms window
centered at the peak latency in the group-average signal. To
determine whether ERPs and MMRs were statistically significant,
the mean amplitudes were compared to zero using two-tailed t-
tests, separately for both groups. Two-tailed t-tests were used to
compare responses between the learning and control groups. Levene’s
test was used to assess the equality of variances and corrected t-
values were used in cases of unequal variances. Effect sizes
(Cohen’s d) were calculated for all between-group comparisons.
Pearson correlation was used to study whether the number of
times the infants had heard the melody affected response
amplitudes. For correlations, coefficients of determinations (R
2
)
are reported.
Results
In newborns and at the age of 4 months, statistically significant
ERPs (see Figure 2, upper and middle panels, and Table 1) were
elicited by all sounds in both groups, with the exception of the late
peak to the unchanged sounds in the learning group at the age of 4
months, which only tended to be statistically significant. Positive
MMRs to changed sounds between 200 and 300 ms after stimulus
onset were statistically significant both in newborns and at the age
of 4 months in both groups (see Figure 2, bottom panels, and
Table 2). The negative MMR peak in 4 month olds was not
statistically significant.
Between-groups comparisons showed that the responses to the
unchanged sounds were larger in the learning than control group both
at birth (t(19) = 2.11, p,0.049, d= 0.97) and at the age of four
months (t(16) = 3.33, p,0.004, d= 1.68). Furthermore, a correla-
tion was found showing that the more often the newborns had
heard the learning CD, the larger the amplitudes to the
unchanged (r = 0.74, p,0.015, R
2
= 0.54) and changed sounds
(r = 0.68, p,0.032, R
2
= 0.46) were. This effect was no longer seen
in the follow-up experiment (p.0.22 for all tests). For MMR
amplitudes, no group differences were found.
Discussion
We investigated the formation and retention of neural
representations induced by exposure to melodies during the fetal
Fetal Music Learning
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Figure 2. ERP and MMR amplitudes in both
learning
(dark bars) and
control groups
(light bars) at birth (left) and at the age of four
months (right). Responses to unchanged sounds were stronger in the learning than control group at birth and at four months of age. Asterisks
denote statistical significances, error bars denote standard errors of the mean.
doi:10.1371/journal.pone.0078946.g002
Table 2. Statistical significances of the ERP and MMR responses for the learning (L) and control (C)groups both at birth and at the
age of 4 months.
Experiment ERPs to unchanged sounds ERPs to changed sounds MMR
Newborns L: t(9) = 6.582*** C: t(10)= 6.827*** L: t(9) = 6.100*** C: t(10) = 6.144*** L: (t(9) = 2.610*
C: (t(10) = 3.279**
4-month olds Early peak L: t(9) = 7.988***
C: t(7) = 6.173***
Late peak L: t(9) = 2.191
Ct(7) = 3.850**
Early peak L: t(9) = 6.475***
C: t(7) = 3.987**
Late peak L: t(9) = 4.280**
C: t(7) = 8.013***
L: t(9) = 4.277**
C: t(7) = 5.095***
Asterisks denote statistical significances.
*: p,0.05, **: p,0.01, ***:p,0.001.
doi:10.1371/journal.pone.0078946.t002
Fetal Music Learning
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period. At birth the learning group had larger ERPs to the melodies
they heard as fetuses than the control group for whom the melodies
were unfamiliar. This difference was still significant at the age of 4
months. Furthermore, ERP amplitudes for unchanged and
changed sounds at birth were correlated with the number of
times the infants in the learning group were exposed to the melody as
fetuses. These results show that fetal exposure to melodic sound
patters can form neural representations which last for several
months. Our results also suggest that the effects of prenatal
exposure are much more long-lasting than reported in the very few
studies conducted previously, which have shown effects from
prenatal exposure lasting for at least six weeks for a melodic
contour [29] with no additional stimulation after birth.
The larger ERPs in the learning than control group cannot be
exclusively explained by possible inborn differences in auditory
processing since ERPs to the changed and unchanged sounds were
correlated with the amount of prenatal exposure. The correlation
effects support the findings of previous studies on learning which
have shown infants and newborns to be extremely fast learners,
capable of learning, for example, statistical regularities of sounds in
2 minutes of stimulation [36]. Furthermore, mere 15 minutes of
unattended exposure to unchanged sounds enhanced the ERP
responses for those sounds in adults [14,37]. However, as the
amount of exposure was correlated with both responses to
changed and unchanged sounds, it may also reflect a nonspecific
effect of music on auditory processing instead of learning of
specific sounds of the melody pattern.
We also found that both the learning and control groups had
statistically significant MMRs to changed sounds in the melody.
Unlike the ERPs for unchanged sounds, the MMR amplitudes did
not differ between the groups. However, in adults the effects of
musical training on MMN are usually seen after active listening to
the melodies, not merely after exposure to melodies [38], and only
a modest enhancement of P2 response amplitude has been shown
after passive musical exposure to those sounds [39,40]. Thus, while
the exposure to melodies may modestly enhance ERP responses
for those sounds, active sensorimotor training seems to be much
more efficient in inducing these changes [39] and such training
might be required for MMR to be enhanced. Alternatively, the
statistically significant MMRs elicited by both groups may reflect
merely physical difference between the changed (all B-notes) and
unchanged notes (mostly other than B-notes).
Taken together, our results show that prenatal exposure to
music can have long-term plastic effects on the developing brain
and enhance neural responsiveness to the sounds used in the
prenatal training, an effect previously only demonstrated in animal
models [41]. Furthermore, we found that these plastic changes are
long lasting, as the effect of prenatal exposure persists for at least
four months without any additional stimulation. These findings
have several practical implications. First, since the prenatal
auditory environment modulates the neural responsiveness of
fetuses, it seems plausible that the adverse prenatal sound
environment may also have long-lasting detrimental effects [8].
Such environments may be, for example, noisy workplaces and, in
case of preterm infants, neonatal intensive care units. Further-
more, as prenatal exposure still affected the ERP responses months
after birth, additional fetal exposure to structured sound environ-
ments might be beneficial for supporting the auditory processing
of, for example, infants at risk for dyslexia in whom basic auditory
processing was shown to be impaired (e.g., [42]). Such effects have
previously been demonstrated in rat pups, showing benefits of
structured sound environments during pregnancy for cortical
organization and synaptogenesis [41], and enhancing their spatial
learning ability for up to 21 days after birth [43]. However, further
studies are needed to shed light on the specific mechanisms of
enhanced neural responsiveness induced by the prenatal stimula-
tion, and to determine whether such stimulation could be used to
alleviate the deficits in auditory processing.
Acknowledgments
We thank research nurse Tarja Ilkka for conducting the newborn EEG
experiments.
Author Contributions
Conceived and designed the experiments: TK MT MH. Analyzed the
data: EP MH TK. Wrote the paper: EP TK MT MH.
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Fetal Music Learning
PLOS ONE | www.plosone.org 6 October 2013 | Volume 8 | Issue 10 | e78946