Memory in the Neonate Brain
Silvia Benavides-Varela1*, David M. Gómez1,2, Francesco Macagno3, Ricardo A. H. Bion4, Isabelle Peretz5,
Jacques Mehler1
1 Cognitive Neuroscience Sector, International School for Advanced Studies (SISSA/ISAS), Trieste, Italy, 2 Center for Advanced Research in Education (CIAE), University of
Chile, Santiago, Chile, 3 Department of Neonatal Pathology, Santa Maria della Misericordia Hospital, Udine, Italy, 4 Department of Psychology, Stanford University,
Stanford, California, United States of America, 5 BRAMS, Université de Montréal, Montréal, Canada
Abstract
Background: The capacity to memorize speech sounds is crucial for language acquisition. Newborn human infants can
discriminate phonetic contrasts and extract rhythm, prosodic information, and simple regularities from speech. Yet, there is
scarce evidence that infants can recognize common words from the surrounding language before four months of age.
Methodology/Principal Findings: We studied one hundred and twelve 1-5 day-old infants, using functional near-infrared
spectroscopy (fNIRS). We found that newborns tested with a novel bisyllabic word show greater hemodynamic brain
response than newborns tested with a familiar bisyllabic word. We showed that newborns recognize the familiar word after
two minutes of silence or after hearing music, but not after hearing a different word.
Conclusions/Significance: The data show that retroactive interference is an important cause of forgetting in the early
stages of language acquisition. Moreover, because neonates forget words in the presence of some –but not all– sounds, the
results indicate that the interference phenomenon that causes forgetting is selective.
Citation: Benavides-Varela S, Gómez DM, Macagno F, Bion RAH, Peretz I, et al. (2011) Memory in the Neonate Brain. PLoS ONE 6(11): e27497. doi:10.1371/
journal.pone.0027497
Editor: Christine Jasoni, University of Otago, New Zealand
Received June 10, 2011; Accepted October 18, 2011; Published November 7, 2011
Copyright: ß 2011 Benavides-Varela 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: The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework
Programme (FP7/2007-2013)/ERC grant agreement nu 269502 (PASCAL) to J.M.; and a grant from Ministerio de Ciencia y TecnologÚa (MICIT) and Consejo Nacional
de Investigaciones Cientı́ficas y Tecnológicas (CONICIT) of Costa Rica to S.B.V. The funding institutions 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: benavide@sissa.it
words. Crucially and differently from previous studies, we focused
on the causes of forgetting in early infancy. We hypothesized that
forgetting of words is higher when the initial encoding event is
followed by similar auditory experiences, creating interference
between the past and present.
In order to test this hypothesis, we familiarized newborns to a
word, and then incorporated different auditory stimuli between the
end of the familiarization period and the onset of the test, hereafter
referred to as the retention interval (see Fig. 1A). A silent retention
interval was our baseline condition to assess memory in the newborn
brain. In order to explore forgetting, we used a novel word or
instrumental music as interfering stimuli. Differences in the amount
of interference caused by a novel word and by music can give
insights into how stimuli in these two auditory domains are
represented in the newborn brain. Speech and music have different
neural encodings in the adult brain [15-16], are acoustically distinct,
and are assumed to be common in the neonate surroundings.
Based on interference theories [17], we pose that if neonates
represent speech and music alike, both stimuli should equally
impair word recognition. Alternatively, if newborns represent
words and instrumental music differently, verbal information
should cause greater interference in word recognition than music.
While previous studies on memory in newborns relied on
behavioral responses, we looked at brain responses instead. fNIRS
is a non-invasive brain imaging technique that measures
hemodynamic responses in the cerebral cortex without requiring
Introduction
Immediately after birth, infants are surrounded by a myriad of
new sounds. For the first time, the newborn brain has access to
enough acoustic detail to distinguish all words in the surrounding
language. Yet, questions related to the parts of speech that can be
remembered and the mechanisms that constrain this capacity have
not been investigated in depth. Can the human brain remember
words heard moments after birth? If so, is the representation of
these words resistant to interfering sounds?
Numerous studies indicate that neonates are sensitive to acoustic
properties of speech and can recognize familiar sounds. Neonates
discriminate between rhythmically different languages [1-3], and they
distinguish all phonetic contrasts in the world’s languages [4-8].
Moreover, neonates prefer a story heard during the last weeks of
pregnancy to a new story [9], and their native language to a foreign
language [10]. However, it is unlikely that fetuses remember details
about the sound forms of words (hereafter referred to as word or words),
because the properties of the uterus render many phonemic
differences imperceptible [11]. There is some evidence that newborns
retain a word over a brief delay [12], and even over a day [13], but it
is not clear how newborns succeeded in these experiments given that
no other study has demonstrated that infants remember common
words from the surrounding language before four months of age [14].
In the present study, we used functional near-infrared
spectroscopy (fNIRS) to investigate neonates’ ability to remember
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Memory in the Neonate Brain
Figure 1. Experimental paradigm and results. A. Schematic diagrams of the procedure used in the experiments. During the familiarization
phase, all the neonates were presented with 10 blocks composed of 6 identical words. A period of silence of varying duration (from 25s to 35s)
followed each block. In the test, 5 blocks of the same word heard during familiarization were presented to half of the neonates while the other half
heard a novel word. In Study 1, a silent 2-minute interval intervened between familiarization and test. In studies 2 and 3, the silent interval was filled
by music (Study 2) or speech stimuli (Study 3). B-C-D) Time courses of the relative hemodynamic changes averaged across all the channels and
subjects per group. The dashed line indicates the time series for the group that heard the same word before and after the pause; the continued line
represents the group that heard a novel word in the test. Error bars indicate standard errors. The x-axis shows number of blocks; in the y-axis the
changes in concentration of Oxy-hemoglobin in mmol*mm is displayed. The neonates who heard a novel word after a silent period showed greater
cortical Oxy-Hb concentration changes in the test than neonates who heard the same word before and after the silent pause. The presence of speech
stimuli during the interval affects recognition memory in neonates. No interference was found when music was presented during the interval
(*, p,0.01; **, p,0.0001).
doi:10.1371/journal.pone.0027497.g001
interval (Fig. 1A), they were presented either with the same word
heard during familiarization (e.g., mita, Same-word condition, also
referred to as familiar word) or a novel CVCV word (e.g., pelu,
Novel-word condition). Notice that the introduction of the 2 min
interval before the test phase differentiates the present work from
previous discrimination studies in which the test immediately
follows the habituation. The familiar and novel words were
recorded by the same speaker and had the same syllabic structure,
stress pattern, duration and intensity (see methods section). The
novel and familiar words were counterbalanced across participants, and no differences in activation were found during
familiarization to the word mita or pelu (permutation tests, all
ps.0.30, see methods section), showing that any difference in the
any overt behavioral response. This property facilitates the
observation of abilities that might have been undetected in
previous behavioral investigations. Recently, several laboratories
have successfully used fNIRS to test precocious auditory
competences in newborns and young infants [18-24].
Results
Study 1: Word recognition after silent intervals
In our first experiment, we used fNIRS to track the functional
hemodynamic responses of the newborn brain when encoding a
consonant-vowel-consonant-vowel (CVCV) word. Neonates were
familiarized with a nonce word (e.g., mita), and after a 2 min silent
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Memory in the Neonate Brain
Study 2: Word recognition after intervening melodies
hemodynamic responses in the test cannot be interpreted merely
as a response to the stimulus. Fifty-six neonates were included in
the analysis.
Results from the test phase indicated that newborns recognized
the familiar word, suggesting that they encoded enough acoustic
detail to distinguish it from the novel word after a silent retention
interval (Fig. 1B). Significant differences in brain activation
between the Same-word and Novel-word conditions were
observed in the first block of the test (permutation tests,
p,0.0001 for oxyHb; p,0.01 for deoxyHb). This was the only
block in which significant differences in brain activity between
neonates in the Novel-word and in the Same-word conditions
were found, in either the familiarization or test phases. In addition,
differences in the responses from the first block of the test and the
last block of the familiarization showed a decrement of oxyHb in
the Same-word condition and an increment in the Novel-word
condition (permutation tests, p,0.01). The concentration of
deoxyHb showed a decrement in the Novel-word condition and
an increment in the Same-word condition (permutation tests,
p,0.01).
In order to determine the brain areas that contributed to the
overall difference found in the test phase, we compared with t-tests
the activation elicited by the two conditions during the first test
block in each of the 24 recording points (Fig. 2). In addition, we
compared brain responses –as measured by oxyHb changes– in six
regions of interest: frontal, temporal, and parietal regions of the
left and right hemispheres (Fig. 3). We observed a main effect of
Condition [ANOVA, F(1,54) = 18.469; p,0.0001] due to the
overall difference in brain activation for neonates in the Novelword condition as compared to neonates in the Same-word
condition. There were no main effects of Hemisphere [ANOVA,
F(1,54) = 1.231; n.s.] or Area [ANOVA, F(2,108) = 1.154; n.s.],
and no significant interactions between factors [all Fs,1]. Our
data show that word recognition evokes a diffuse cortical response
in the neonate brain, which is bilaterally spread over temporal,
parietal, and frontal areas. Because fNIRS is not suitable to
measure changes in deeper brain areas, whether or not the
observed pattern of activation is partially responsible for word
recognition should be clarified in future studies.
These results show that the newborn brain is able to encode a
word from brief exposure. Exposure for over half an hour -or over
two hundred repetitions of the words- was used in previous studies
looking at memory in newborns [12,13]. The familiarization phase
of our experiment was much shorter (six minutes in total, including
more than four minutes of silent pauses) and with fewer instances
of the familiarization word, providing evidence that newborns do
not require protracted experience to remember a word.
The question arises as to the level of detail that the newborns
remembered. Did they retain a holistic representation of the word?
Were some syllables or phonemes better encoded than others?
Was only some information about the word or its syllables (onset,
nucleus) encoded? Whereas in the current study, the familiar and
the novel words had entirely different sets of phonemes, future
studies with words sharing only some syllables or phonemes will be
able to establish the detail with which the newborn brain encodes
speech stimuli. Still, our study provides some first insights about
the information newborns store when they hear words. Neonates
maintain the representation of a CVCV word (or parts of it) over
the silent retention interval and compare this representation with
the sound of a new CVCV word presented during test.
Importantly, the two words are pronounced by the same speaker
and have similar acoustic properties, suggesting that the
information encoded by newborns goes beyond low-level perceptual features such as pitch, voice quality, duration, or intensity.
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Despite the recognition capacity demonstrated in Study 1,
newborns’ early experiences take place in surroundings that are
very different from the silent environment used in our study. Thus,
in studies 2 and 3, we investigated whether newborns’ memory for
words could withstand interfering auditory stimuli.
In Study 2, a new group of neonates (divided again in Sameword and Novel-word conditions) encountered new auditory
stimuli during the retention interval. In this study, an excerpt of
instrumental music was played between familiarization and test.
Under these circumstances, a recognition response would
demonstrate that neonates were able to remember a word, and
could overcome the interference from music (see details in the
method section).
Our results show that newborns remembered the new word
despite the intervening melody (Fig. 1C). As in Study 1, significant
differences in hemodynamic activity between conditions were
found exclusively in the first block of the test phase; participants in
the Novel-word condition showed greater concentrations of
oxyHb than participants of the Same-word condition (permutation
tests, p,0.01). A distributed network including temporo-parietal
and frontal areas was again responsible for the observed difference.
Furthermore, changes in oxyHb concentration between the last
block of the familiarization and the first block of the test differed
between the two conditions (permutation tests, p,0.05). Participants in the Same-word condition showed a decrease in
concentration of oxyHb between familiarization and test, while
participants in the Novel-word condition displayed increased
hemodynamic responses (Fig. 4A). The oxyHb concentration in
the first block of the test was significantly different between
conditions (ANOVA, main effect of Condition [F(1,26) = 19.318;
p,0.0001]). There was no main effect of Hemisphere [ANOVA,
F(1,26) = 0.058; n.s.], Area [ANOVA, F(2,52) = 0.011; n.s.], and
no significant interactions between factors [all Fs,1]. As in the
previous study, participants assigned to the Same-word and Novelword conditions did not differ during the familiarization phase.
These results confirm that newborns are able to recognize a
familiar word after a retention interval of a few minutes. In
addition, this study shows that newborns represented the word in a
format that can resist interference from music.
However, these results do not necessarily imply that this word
representation would resist interference from more similar
auditory stimuli. In fact, previous studies with adults have
suggested that auditory stimuli suffer from highly specific
interference effects (e.g. listening to tones interferes with the
memory of previously heard tones, but listening to digits does not,
[25]). Therefore, in Study 3 we asked whether newborns
represented the word in a format that could resist interference
from another word.
Study 3: Word recognition after intervening speech
In Study 3 we tested a new group of newborns with a paradigm
identical to the one used in Study 2, except that we presented the
word noke (instead of instrumental music) during the retention
interval. In this study, we hypothesized that the speech stimuli
would cause greater interference than the music used in Study 1,
possibly causing newborns to forget the word heard during
familiarization. This result would suggest additionally that words
and music are processed differently in the newborn brain.
In contrast with our previous results, we found no evidence that
newborns recognized the familiarization word. We found no
significant differences between the conditions in the test phase
(Fig. 1D). We also failed to observe significant variations in
oxyHb-concentration between the last familiarization block and
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Memory in the Neonate Brain
Figure 2. Statistical maps on the schematic neonate brain. The graph depicts the comparison between the Novel-word and Same-word
conditions in the first block of the test -block 11, Study 1-. Significance levels for each channel (p-values corrected by false discovery rate [38]) are
color-coded as indicated on the color bar. Grey circles indicate no significant differences between conditions.
doi:10.1371/journal.pone.0027497.g002
predicts that a humming melody produced by the vocal tract would
interfere with the memory for words. As a third alternative,
similarity between music and speech might be computed at abstract
levels that are processed by specialized brain mechanisms. The
second and third alternatives are supported by studies showing that
the neonate brain is specialized to process speech [22,26].
Additional support for these alternatives comes from studies
showing that speech and music are treated differently in the human
brain [15-16,27-28], and that vocal and non-vocal sounds are
processed by different brain areas [22,29-30].
Newborns are able to remember a word, but how are these words
encoded? Linguists and psychologists have proposed that speech is
encoded as sequences of articulatory gestures [31-32], as features,
phonemes, syllables, or prosody [33-36]. Future studies should focus
on the nature of speech encoding at birth. Whatever this encoding
might be, it probably does not generalize to music sequences [15-16].
Here we provide evidence that humans are able to memorize
words hours after birth. Our findings also suggest that interference
is one of the causes of forgetting in early infancy. The word and
the instrumental music used during the retention interval elicit
different processes in the neonate brain. Future studies should
investigate whether this differential processing and interference
generalizes to a broader variety of speech and melodies,
determining the extent to which the human brain is pre-wired to
interpret the auditory world.
the first block of the test phase (permutation test, p.0.50)
(Fig. 4B). Together these results suggest that the presence of
another word in a portion of the retention interval disrupted
newborns’ ability to recognize the previously heard word. As in the
previous studies, we found no significant differences during the
familiarization phase.
Discussion
In laboratory studies, newborns can retain the sounds of words
[12,13], but there is no evidence in the literature showing that
infants younger than 4 months of age can remember words from
their surrounding language. In this work, we found hemodynamic
responses correlated with word recognition in the neonate brain.
Our studies also suggest possible causes of forgetting in very young
infants. In Study 1, we showed that newborns familiarized with a
bisyllabic word distinguished it from a novel word. Brain responses
measured with fNIRS revealed a significant recognition response
when familiarization and test phases were separated by a 2minutes silent retention interval.
Studies 2 and 3 focused on the role of interference on forgetting.
Study 2 demonstrates that the neonate brain recognizes a word
after exposure to instrumental music, whereas Study 3 shows that
this memory trace is diminished when a different word is presented
before the test. As we hypothesized, newborns’ memory for words
is affected when it is followed by similar auditory stimuli.
An interesting area for speculation constitutes the level over
which the newborn brain computes similarity between speech and
music. What counts as similar auditory stimuli for newborns? As a
first alternative, it is possible that similarity is computed with
reference to low-level acoustic cues. The word presented during the
familiarization and retention interval had the same pitch, duration,
intensity, voice quality, syllabic structure, and stress pattern. In
contrast, the instrumental music had a more complex melodic
contour and continuous transitions. This alternative predicts that it
is the degree of similarity –acoustic, but not phonemic– between the
familiarization word and the intervening word that determines the
amount of interference. A second alternative is that similarity might
be computed with reference to the source that produced the
auditory stimuli. Words are generated by the vocal tract, while
instrumental melodies are produced by artifacts. This alternative
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Methods
Participants
Fifty-six neonates (27 females, mean age 3.1 days, range 1-5
days) were included in Study 1. Thirteen additional neonates were
tested but excluded from the analysis because of head movements
that produced large motion artifacts (n = 7), or because they cried
before the end of the experiment (n = 6). In Study 2, 28 healthy
full-term neonates (15 females, mean age 2.8 days, range 1-5 days)
participated in the experiment. Five neonates were tested but
excluded from the analysis because head movements produced
large motion artifacts (n = 3), or because of crying before the end
of the experiment (n = 2). Finally, in Study 3, 28 new healthy fullterm neonates (12 males, mean age 2.9 days, range 1-5 days) were
included in the analysis. Eight additional neonates were tested but
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Memory in the Neonate Brain
Figure 4. OxyHb changes from the last familiarization block to
the first test block (Studies 2 and 3). A. When the 2-minute pause
was filled with music, channels in both hemispheres showed a
decrement in the concentration of oxyHb from the familiarization to
the test in the Same-word condition, and an increment in the Novelword condition. B. There were no significant changes in oxyHb
concentration from the familiarization to the test phases when the
interval was filled with speech stimuli.
doi:10.1371/journal.pone.0027497.g004
had thick hair. Neonates were recruited at the newborn nursery of
Azienda Ospedaliera Universitaria Santa Maria della Misericordia
in Udine, Italy. Neonates were considered eligible if they had
gestational ages between 38 and 42 weeks, Apgar scores $8 in the
first minute and diameter of head $33.5 cm. Bioethics Committee
of SISSA/ISAS (International School for Advanced Studies)
approved the study; all parents signed an informed consent before
the experiments.
Stimuli
The three pseudo words used (mita, pelu, noke) were pronounced
using a neutral intonation, carried first syllable stress, had a CVCV
(consonant-vowel-consonant-vowel) structure, and were edited to
have the same intensity (70dB) and duration (700 ms). An adapted
excerpt of a Brahms’ waltz played on a piano was used in Study 2.
Its duration was 10 s (the same length of a block composed of 6
words) and had a mean intensity of 70dB.
Figure 3. OxyHb changes from the last familiarization block to
the first test block (Study 1). Channels bilaterally located in frontal,
temporal and parietal areas show a decrease in the concentration of
oxyHb when neonates hear the same word before and after the pause
(white bar). In contrast, when neonates are confronted with a novel
word in the test (black bar) the concentration from the familiarization
phase to the test increases. Colored ellipses on the schematic neonate
brain indicate the localization of the channels included in the areas of
interest.
doi:10.1371/journal.pone.0027497.g003
Procedure
The experiment consisted of a familiarization phase, an interval,
and a test phase (Fig. 1A). The familiarization phase lasted six
minutes and was organized in ten blocks. Each block contained six
identical words. Within blocks, words were separated by pauses of
randomized length (0.5 s or 1.5 s), yielding blocks of approximately
10 s each. Blocks were separated by time intervals of varying duration
(25 s or 35 s). A 2-minute interval was inserted between the end of the
familiarization and the beginning of the test phase. The interval in
excluded from the analysis because movements produced large
motion artifacts (n = 7), or because of crying before the end of the
experiment (n = 1). We failed to obtain signals from neonates who
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To assess whether the two conditions differed across the
familiarization phase, we computed the maximum difference
between the mean activation for each condition. That is to say, for
each block b = 1,2,…, we calculated
Study 1 was a silent interval. In Study 2, thirty seconds were occupied
by three blocks of Brahms’ lullaby. In Study 3, this interval was
occupied by three blocks of another word. The test consisted of five
blocks (3 minutes). Neonates were tested while lying in their cribs,
asleep or in a state of quiet rest. A nurse assisted neonates inside a
dimly lit sound-attenuated booth where the experiment was run.
Sound stimuli were presented via two loudspeakers placed at a
distance of 1.2 m from the infant’s head at a 30u angle on both sides,
raised to the same height as the crib. The speakers were connected to
a Macintosh power PC G5 computer that at the same time operated
the NIRS machine and presented the auditory stimuli using PsyScope
X software (http://psy.ck.sissa.it/). Both the NIRS machine and the
computer were placed outside the experimental booth and were
controlled by the experimenter. An infrared video camera was used
to monitor the infant’s behavior.
For half of the participants in each experiment, the stimulus of
the familiarization phase was mita and the novel word in the test
was pelu. For the other half of participants, the words were
exchanged, so that pelu was used during the familiarization phase
and mita was presented as the novel word in the test. All analyses
used pooled data from all newborns, since there was no significant
difference between participants in any of the blocks (permutation
test, all ps.0.30), evidencing that the acoustic properties of the
words per se are not responsible for different neural responses.
Diff(b)~ max DA1 (b,c){A2 (b,c)D
c~1,:::,24
where Aj (b,c) is the activation in block b and channel c, averaged
among all neonates assigned to condition j (Same-word/Novelword). When analyzing the familiarization phase as a whole, we
further computed Diff(fam) as the maximum of Diff(b) for all
blocks b = 1,2,…,10. Because the distribution of this statistic is not
Gaussian, we evaluated significance using non-parametric methods. Specifically, we used permutation tests [37]. In these tests, a
distribution for the test statistic under the null hypothesis is
obtained by re-randomizing the condition assigned to each
subject. Assuming that the two conditions do not differ during
the familiarization phase, then the distribution of Diff(fam) is the
same for the original group assignment as for any random
reassignment. Significance is then computed as the proportion of
reassignments exhibiting a value of Diff(fam) greater or equal than
the one associated to the original groups. Other statistics such as
Diff(test) are built and statistically evaluated in the same way. We
used 10,000 random reassignments for each permutation test.
Additional tests were conducted to identify the channels
contributing to the differences in the test phase that the previous
analysis found. We compared the two groups on a channel-bychannel basis using 2-sample t-tests. To solve the problem of
multiple comparisons, we computed corrected p-values based on
the procedure proposed in [38; Theorem 1.3] to control the False
Discovery Rate at the 5% level. That is, starting from the 24
uncorrected p-values (one per channel) p(1), p(2), …, p(24) sorted
Data acquisition
A NIRS machine (ETG-4000, Hitachi Medical Corporation,
Tokyo, Japan) was used. The separation between emitters and
detectors was 3 cm and the sampling rate 10 Hz. The total laser
power output per fiber was 0.75 mW and the two continuous light
sources used 695 nm and 830 nm wavelengths. Probes holding the
fibers were placed on the neonate’s head by using skull landmarks. We
obtained simultaneous recordings from 24 points (channels). Although
individual variation cannot be excluded, placement maximizes the
likelihood of monitoring the temporal, parietal and frontal areas.
Channels from 1 to 12 were placed on the left hemisphere and from
13 to 24 on the right hemisphere. Channels 1, 2, 4 and 5 were roughly
located in the left frontal regions; 3, 6, 8 and 11 in the left temporal
and 7, 9, 10 and 12 in the left parietal region. Channels 13, 14, 15 and
16 were in the right frontal area; Channels 17, 19, 22 and 24 in the
right temporal and 18, 20, 21 and 23 in the right parietal region.
from smallest to largest, corrected p-values were obtained as
24:c(24)
p(k) , with c(24) defined as 1+1/2+1/3+…+1/24.
pFDR
(k) ~
k
To examine
larger brain areas associated with auditory
memory, we compared activation during the last block of the
familiarization phase in frontal, temporal and parietal areas. We
used a repeated-measures analysis of variance (ANOVA) with
Condition (Same-word/Novel-word) as a between-subject factor
and Area (frontal/temporal/parietal) and Hemisphere (left/right)
as within-subject factors. Two channels were included in each
area-hemisphere region. In the left frontal, channels 2 and 5; left
temporal, 3 and 6; left parietal, 7 and 9; right frontal, 13 and 15;
right temporal, 17 and 19; and right parietal, 18 and 21. These
channels were chosen based on previous imaging studies of
auditory processing in neonates and young infants [19].
Data Processing and Analysis
Our analysis was based on the variations in oxy-hemoglobin
(oxyHb) concentrations assessed on the basis of the light
absorption recorded by the NIRS machine. The signal was
band-pass filtered between 0.02 Hz and 1.00 Hz to remove
components arising from slow fluctuations of cerebral blood flow,
heartbeat and other possible artifacts. Single blocks from specific
channels were eliminated on the basis of two criteria: 1) light
absorption of less than 1% of the total light emitted (generally
because the probes were not touching the neonate’s scalp); 2) the
presence of large movement artifacts. The criterion to detect
artifacts was the presence of rapid changes in the signal
(.0.1 mmol*mm in an interval of 0.2 s). Blocks with more than
12 rejected channels were excluded. Participants were included in
the analysis only if the amount of data rejected was less than 30%.
For the non-rejected blocks, a baseline trend was linearly fitted
between the mean of the 5 s preceding the onset of the block and the
mean of the 5 s between the 25ths and the 30ths after the onset of the
block. For each channel, the mean signal changes in the period
between the end of the auditory stimulation and the following 9s
(where the maximum amplitudes of the hemodynamic responses are
expected) were used to carry out the subsequent statistical analysis.
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Acknowledgments
We thank the personnel of Udine Hospital’s Neonatology and Obstetrics
departments for their valuable assistance on the recruitment of neonates.
Our gratitude also goes to the parents of the newborns for their participation.
We are grateful to BRAMS for preparing the melodies and to Susana Frank
and John Nicholls for their corrections to our manuscript. We acknowledge
the technical and administrative support provided by Alessio Isaja, Marijana
Sjekloca and Francesca Gandolfo. We thank the present and former
members of SISSA-LCD Lab for their support, helpful comments and
assistance in the preparation of this manuscript.
Author Contributions
Conceived and designed the experiments: SB-V RAHB JM. Performed the
experiments: SB-V DMG FM. Analyzed the data: DMG SB-V. Wrote the
paper: SB-V DMG RAHB IP JM.
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November 2011 | Volume 6 | Issue 11 | e27497