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Mother’s voice and heartbeat sounds elicit auditory plasticity in the human brain before full gestation


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Significance Newborns can hear their mother’s voice and heartbeat sounds before birth. However, it is unknown whether, how early, and to what extent the newborn's brain is shaped by exposure to such maternal sounds. This study provides evidence for experience-dependent plasticity in the auditory cortex in preterm newborns exposed to authentic recordings of maternal sounds before full-term brain maturation. We demonstrate that the auditory cortex is more adaptive to womb-like maternal sounds than to environmental noise. Results are supported by the biological fact that maternal sounds would otherwise be present in utero had the baby not been born prematurely. We theorize that exposure to maternal sounds may provide newborns with the auditory fitness necessary to shape the brain for hearing and language development.
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Mothers voice and heartbeat sounds elicit auditory
plasticity in the human brain before full gestation
Alexandra R. Webb
, Howard T. Heller
, Carol B. Benson
, and Amir Lahav
Department of Pediatrics Newborn Medicine and
Department of Radiology, Brigham and Womens Hospital, Boston, MA 02115; and
Department of
Pediatrics, MassGeneral Hospital for Children, Harvard Medical School, Boston, MA 02115
Edited by Mortimer Mishkin, National Institute for Mental Health, Bethesda, MD, and approved January 28, 2015 (received for review August 6, 2014)
Brain development is largely shaped by early sensory experience.
However, it is currently unknown whether, how early, and to
what extent the newborns brain is shaped by exposure to mater-
nal sounds when the brain is most sensitive to early life program-
ming. The present study examined this question in 40 infants born
extremely prematurely (between 25- and 32-wk gestation) in the
first month of life. Newborns were randomized to receive auditory
enrichment in the form of audio recordings of maternal sounds
(including their mothers voice and heartbeat) or routine exposure
to hospital environmental noise. The groups were otherwise medi-
cally and demographically comparable. Cranial ultrasonography
measurements were obtained at 30 ±3 d of life. Results show that
newborns exposed to maternal sounds had a significantly larger
auditory cortex (AC) bilaterally compared with control newborns re-
ceiving standard care. The magnitude of the right and left AC thick-
ness was significantly correlated with gestational age but not with
the duration of sound exposure. Measurements of head circumfer-
ence and the widths of the frontal horn (FH) and the corpus callosum
(CC) were not significantly different between the two groups. This
study provides evidence for experience-dependent plasticity in the
primary AC before the brain has reached full-term maturation. Our
results demonstrate that despite the immaturity of the auditory path-
ways, the AC is more adaptive to maternal sounds than environmen-
tal noise. Further studies are needed to better understand the neural
processes underlying this early brain plasticity and its functional impli-
cations for future hearing and language development.
mothers voice
preterm newborns
One of the first acoustic stimuli we are exposed to before
birth is the voice of the mother and the sounds of her
heartbeat. As fetuses, we have substantial capacity for auditory
learning and memory already in utero (15), and we are partic-
ularly tuned to acoustic cues from our mother (69). Previous
research suggests that the innate preference for mothers voice
shapes the developmental trajectory of the brain (10, 11). Pre-
natal exposure to mothers voice may therefore provide the brain
with the auditory fitness necessary to process and store speech
information immediately after birth (12, 13).
There is evidence to suggest that prenatal exposure to the ma-
ternal voice and heartbeat sounds can pave the neural pathways in
the brain for subsequent development of hearing and language
skills (14). For example, the periodic perception of the low-fre-
quency maternal heartbeat in the womb provides the fetus with an
important rhythmic experience (15, 16) that likely establishes the
neural basis for auditory entrainment and synchrony skills necessary
for vocal, gestural, and gaze communication during motherinfant
interactions (17, 18).
Studies examining the neural response to the maternal voice
soon after birth have found activation in posterior temporal
regions, preferentially on the left side, as well as brain areas
involved in emotional processing including the amygdala and
orbito-frontal cortex (19). Similarly, Beauchemin et al. have
found activation in language-related cortical regions when new-
borns listened to their mothers voice, whereas a strangers voice
seemed to activate more generic regions of the brain (20). In
addition, Partanen et al. have shown that the neural response to
maternal sounds depends on experience as full-term newborns
react differentially to familiar vs. unfamiliar sounds they were
exposed to as fetuses, suggesting correlation between the amount
of prenatal exposure and brain activity (21). Taken together, the
above studies suggest that the mothers voice plays a special role
in the early shaping of auditory and language areas of the brain.
Numerous animal studies have shown that brain development
relies on developmentally appropriate acoustic stimulation early
in life (2232). Auditory deprivation during critical periods can
adversely affect brain maturation and lead to long-lasting neural
despecialization in the auditory cortex (AC), whereas auditory
enrichment in the early postnatal period can enhance neural
sensitivity in the primary AC, as well as improve auditory recog-
nition and discrimination abilities.
Preterm infants are born during a critical period for auditory
brain development. However, the maternal auditory nursery pro-
vided by the womb vanishes after a premature birth as the preterm
newborn enters the neonatal intensive care unit (NICU). The
abrupt transition of the fetus from the protected environment of the
womb to the exposed environment of the hospital imposes signifi-
cant challenges on the developing brain (33). These challenges have
been associated with neuropathologic consequences, including re-
duction in regional brain volumes, white matter microstructural
abnormalities, and poor cognitive and language outcomes in pre-
term compared with full-term newborns (3441).
Considering the acoustic gap between the NICU environment
and the womb, it is not surprising that auditory brain development
is compromised in preterm compared with full-term infants (42,
43). Numerous studies have suggested that the auditory environ-
ment available for preterm infants in the NICU may not be con-
ducive for their neurodevelopment (4447). These concerns are
Newborns can hear their mothers voice and heartbeat sounds
before birth. However, it is unknown whether, how early, and to
what extent the newborns brain is shaped by exposure to such
maternal sounds. This study provides evidence for experience-
dependent plasticity in the auditory cortex in preterm newborns
exposed to authentic recordings of maternal sounds before full-
term brain maturation. We demonstrate that the auditory cortex is
more adaptive to womb-like maternal sounds than to environ-
mental noise. Results are supported by the biological fact that
maternal sounds would otherwise be present in utero had the baby
not been born prematurely. We theorize that exposure to maternal
sounds may provide newborns with the auditory fitness necessary
to shape the brain for hearing and language development.
Author contributions: A.R.W., H.T.H., C.B.B., and A.L. designed research; A.R.W., H.T.H.,
and A.L. performed research; A.R.W., H.T.H., C.B.B., and A.L. contributed new reagents/
analytic tools; A.R.W., H.T.H., and A.L. analyzed data; and A.R.W., H.T.H., C.B.B., and A.L.
wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
To whom correspondence should be addressed. Email: PNAS Early Edition
derived from the frequent reality that hospitalized preterm new-
borns are overexposed to loud, toxic, and unpredictable environ-
mental noise generated by ventilators, infusion pumps, fans,
telephones, pagers, monitors, and alarms (4851), whereas at the
same time they are also deprived of the low-frequency, patterned,
and biologically familiar sounds of their mothersvoiceand
heartbeat, which they would otherwise be hearing in utero (33, 45).
In addition, the hospital environment contains a significant amount
of high-frequency electronic sounds (52, 53) that are less likely to
be heard in the womb because of the sound attenuation provided
by maternal tissues and fluid within the intrauterine cavity (5456).
Efforts to improve the hospital environment for preterm neonates
have primarily focused on reducing hospital noise and maintaining
a quiet environment. However, exposing medically fragile preterm
newborns to low-frequency audio recordings of their mothers on
a daily basis has been less acknowledged to be of necessity, and the
extent to which such maternal sound exposure can influence brain
maturation after an extremely premature birth has been a matter
of much debate.
The present study aimed to determine whether enriching
the auditory environment for preterm newborns with authentic
recordings of their mothers voice and heartbeat sounds in the
first month of life would result in structural alterations in the
AC. The rationale driving this question lies in the fact that
such enriched maternal sound stimulation would otherwise be
present had the baby not been born prematurely.
As shown in Table 1, the maternal sounds and control groups did
not significantly differ in the following characteristics: sex, birth
gestational age, birth weight, 1-min Apgar, 5-min Apgar, head
circumference and postmenstrual age at 1-mo cranial ultrasound,
days on mechanical ventilation, and administration of antenatal
Results were based on structural measurements of the AC, the
frontal horn (FH), and the corpus callosum (CC) obtained by
cranial ultrasonography (Fig. 1). AC thickness was significantly
different between the groups [F(2, 37) =10.10, P<0.001] (Fig. 2).
Infants in the maternal sounds group had a significantly larger right
and left AC compared with infants in the control group [F(1, 38) =
20.45, P<0.001 and F(1, 38) =6.55, P=0.015, respectively]. The
width of the FH and the CC were not significantly different
between the two groups [F(2, 37) =0.90, P=0.413 and t(38) =
0.56, P=0.578, respectively] (Fig. 2 and Table 2).
Spearman correlational analysis revealed that, in both groups,
the magnitude of the right and left AC thickness was signifi-
cantly correlated with gestational age (for right AC and gesta-
tional age: maternal sounds: ρ=0.55, P=0.01; controls:
ρ=0.60, P=0.007; and for left AC and gestational age: maternal
sounds: ρ=0.56, P=0.008; controls: ρ=0.51, P=0.02). The
measurements of the control brain regions (FH and CC) were not
significantly correlated with gestational in either group.
Finally, within the maternal sound group, the average duration
of sound exposure was 23.6 d with a narrow distribution (SD =
3.4), which was insufficient to significantly correlate with any of
the AC measures (right AC: ρ=0.12, P=0.59; left AC: ρ=
+0.09, P=0.68).
This study examined the effect of sound exposure on brain de-
velopment in hospitalized preterm newborns. We compared the
exposure effects between unfiltered hospital noise (currently the
standard of care) vs. a modified care practice, which includes daily
auditory enrichment in the form of low-pass filtered recordings of
mothers voice and heartbeat sounds. Our results demonstrate au-
ditory brain plasticity induced by exposure to womb-like maternal
sounds in preterm newborns. Newborns receiving added exposure
to mothers voice and heartbeat sounds in the early postnatal period
showed significantly larger AC at 1 mo of age compared with
control newborns receiving routine care. The magnitude of the
right and left AC thickness was significantly correlated with ges-
tational age at birth. The negative direction of the correlations
indicates that younger babies had larger AC measurements relative
to the transtemporal diameter (TTD) of their brain, suggesting
that the relative size of AC is more pronounced earlier in gesta-
tion. As we discuss below, this study illustrates a highly specific
modifiability within the AC in response to maternal sounds and
highlights the importance of the newborns sensory experience
during postnatal hospitalization.
Our findings of auditory brain plasticity before full gestation
are in keeping with several studies, primarily by Merzenich and
colleagues, showing that early auditory experience, either in the
form of enrichment or impoverishment, can have a substantial
impact on both the structural and functional development of the
AC in rat pups (26, 27, 29, 31, 57, 58). Similarly, an established
body of work by Lickliter and colleagues has shown that
Table 1. Newborn characteristics
Parameters Maternal sounds Control Pvalue
Subjects, n21 19 NA
Female, n(%) 9 (43) 4 (21) 0.141
Birth GA (wk) 28.9 ±1.9 29.6 ±2.1 0.262
Birth weight (g) 1,310 ±344 1,397 ±369 0.441
1-min Apgar 5.48 ±2.50 5.26 ±1.91 0.766
5-min Apgar 7.29 ±1.52 7.68 ±1.00 0.537
HC at 1-mo cUS (cm) 29.3 ±2.6 29.9 ±2.8 0.481
PMA at 1-mo cUS (wk) 33.06 ±1.92 33.87 ±2.12 0.211
Mechanical ventilation (d) 2.52 ±2.87 3.47 ±8.08 0.616
Antenatal corticosteroids, n(%) 13 (62) 11 (58) 0.796
cUS, cranial ultrasound; GA, gestational age; HC, head circumference;
NA, not applicable; PMA, postmenstrual age.
Fig. 1. Shown are measurements (white lines) of the (A) thickness of the AC in the coronal plane, (B) width of the FH of the lateral ventricle in the coronal
plane, and (C) width of the body of the CC in the midsagittal plane.
| Webb et al.
bobwhite quail chicks receiving auditory stimulation early in
embryogenesis demonstrated improved auditory learning and
memory when tested postnatally (5961). The collective im-
pression of the above studies indicates that the early postnatal
period provides a critical window of opportunity wherein sensory
enrichment or sensory deprivation can play a major role in the
development of the auditory brain system.
It is important to highlight that newborns in the maternal
sound group were exposed to premixed audio recordings that
included both the maternal voice and the maternal heartbeat
played at the same time, much like they would have otherwise
experienced had they not been born prematurely and were still in
the womb. The concurrent inclusion of both the maternal
heartbeat and the maternal voice on a single audio track was
necessary to simulate the in utero experience, consistent with
previous protocols used in recent studies from our laboratory
(62, 63). Therefore, the present study cannot determine the
relative contribution of mothers voice vs. the maternal heartbeat
to the observed effects on auditory brain development.
To add an additional layer of biological authenticity to our
maternal sound stimulation, newborns in the maternal sound
group were intentionally exposed to a low-pass filtered version of
the maternal sounds recordings, which naturally eliminated most
segmental speech information. Low-pass filtering usually dis-
rupts the intelligibility of individual syllables and speech rate in
the utterances, and the resulting muffledness makes prosody the
primary acoustic element contributing to auditory perception
(64, 65). It is therefore tempting to speculate that the sole pro-
sodic information of the maternal sounds stimulus was sufficient
to yield the observed increase in cortical thickness of the AC
among our preterm newborn listeners. Prosodic features, such as
melody, intensity, and rhythm, are known to be essential for
language acquisition, and there is compelling evidence to suggest
that newborns are strongly influenced by prosodic features of
their native language long before first words are even produced
(6669). The question of whether daily exposure to unfiltered
maternal sounds would result in different structural patterns
of brain maturation is still unclear and needs to be investigated
in future studies.
Our results suggest that daily exposure to biologically mean-
ingful acoustic stimulation in the form of mothers voice and
heartbeat sounds, even for a relatively short duration of time (i.e.,
3 h/d), was yet sufficient to yield structural changes in the de-
veloping auditory cortex. One should bear in mind that for the vast
majority of the time, newborns in the maternal sounds group were
exposed to routine noises in the hospital environment, much like
infants in the control group. The exposure difference between the
groups comes down to only 3 h of recorded maternal sound ex-
posure per day. It is therefore striking that newborns exposed to
recorded maternal sounds demonstrated significant microstruc-
tural plasticity in the AC with minimal dosage and within less than
1 mo of exposure. These rapid changes are particularly interesting
given that the rate of microstructural brain maturation in preterm
newborns has been previously correlated with cortical growth, and
predicted higher developmental test scores at 2 y of age (70).
Although the auditory brain system undergoes experience-
dependent plasticity across the lifespan (71), it is theorized that
the probability of such plasticity may be higher and much needed
during critical periods when the underlying developmental pro-
cesses are still in flux, such as following a premature birth. In
future studies, it would be interesting to test whether added ex-
posure to maternal sounds in the early postnatal period can better
facilitate synaptic pruning and neural migration in the AC than
exposure to hospital environmental noise, a question that was
beyond the scope of the present study and is yet to be determined.
Notably, exposure to maternal sounds in our study did not
seem to influence overall brain growth, but instead led to a
rather region-specific structural plasticity in the AC, a brain area
that is most intuitively expected to be affected by the auditory
stimulation. The fact that both newbornshead circumference
(Table 1) and the width of the lateral ventricular horns (Table 2)
measures that have been previously correlated with total brain
tissue volume (72)did not significantly differ between the groups
may be taken as evidence that the neuroplasticity induced by
maternal sounds did not appear to increase overall brain matter,
consistent with the specialized nature of experience-dependent
plasticity (73, 74).
The possibility that newborns in the control group had smaller
AC to begin with has been ruled out by our method of analysis,
by which we normalized the size of the AC for each infant based
on the TTD of the brain. This normalized measure represents
the cortical thickness of the AC compared with the size of the
brain, accounting for any possible differences between the
groups in AC size before the study onset. Future ultrasonogra-
phy studies, using a volume probe and a repeated-measure de-
sign over a longer period are needed to determine the effects of
exposure to maternal sounds on total brain volume at term-
equivalent age and beyond.
The bilateral plasticity in the AC is noteworthy. Given the
linguistic nature of the stimulus the newborns were exposed to
(i.e., maternal speech sounds), one might expect the effect to be
primarily on the left side of the brain because of the functional
lateralization typically seen in the adult brain when processing
speech (7578). However, it is possible that because the preterm
newborns in our study were at a very early stage of development,
essentially at an age equivalent to the last trimester of pregnancy
and before full gestation, their brains had not yet begun to ex-
hibit hemispheric specialization for speech, and thereby auditory
neuroplasticity occurred more globally on both sides of the AC.
Size normalized by TTD
Brain structures
Maternal Sound
Fig. 2. Mean brain measurements are shown for the maternal sounds (blue)
and control (red) groups in normalized arbitrary units, including the right
and left AC thickness (R-AC and L-AC), right and left FH width (R-FH and
L-FH), and width of the body of the CC. All measurements were individually
normalized by the transtemporal diameter (TTD) of the newborn. Error bars
represent SD. Asterisks denote statistically significant results (P<0.05); values
are given in Table 2.
Table 2. Anatomical size of brain structures
Brain structure (width) Maternal sounds Control Pvalue
Auditory cortex
R-AC 4.16 ±0.94 3.11 ±0.44 0.000
L-AC 3.62 ±0.95 2.96 ±0.68 0.015
Frontal horn
R-FH 1.50 ±1.07 2.00 ±1.66 0.270
L-FH 2.15 ±1.20 2.31 ±1.75 0.723
Corpus callosum 4.72 ±0.64 4.59 ±0.73 0.578
Measurements normalized for each infant by the TTD.
Webb et al. PNAS Early Edition
An alternative hypothesis to explain the bilateral plasticity in the
AC in the present study can be supported by a growing body of
research, suggesting that the apparent left-sided lateralization
for speech and language processing, specifically in the AC, is not
an absolute dominance but rather a shared expertise by the two
hemispheres (7981). The above hypotheses must be made with
caution because at this premature age, cortical folding is still in
flux and the majority of neurons are still migrating and have not
yet reached their final cortical destination. Thus, brain imaging
at this age can only provide a snapshot in time of the current
developmental course and no firm conclusions regarding per-
manent hemispheric dominancy can be drawn based on the
present study. In addition, the early onset of left hemispheric
differentiation in newborns is primarily based on functional
rather than structural evidence. Previous studies in preterm
neonates have found left-hemispheric functional advantage for
speech processing in the posterior temporal region, as indicated
by faster and more sustained responses to speech sounds over the
left than over the right hemisphere (82). These findings are
consistent with similar results suggesting that infants are born with
a left hemisphere functional specialization for speech processing
(8385). The ultrasound data obtained in our study are solely based
on structural measurements, and thus our findings cannot dispute or
support the above-mentioned studies. However, our results indicate
that newborns in the maternal sounds group had larger AC on the
right compared with the left side of the brain (Fig. 2). Although this
difference was not statistically significant, it is congruent with pre-
vious evidence showing that many sulci appear 12 wk earlier on the
right than on the left side of the brain, with larger temporal sulci on
the right hemisphere (86, 87).
Interestingly, we found no differences in CC size between the two
groups of newborns in our study. The CC was chosen as a control
region because of its central location and global role in inter-
hemispheric communication, connecting the auditory areas be-
tween the two hemispheres (88). In addition, because the size of the
CC is known to correlate with overall brain volume, we assumed
that the CC may have a good predictive value for experience-
dependent changes of global brain growth (89). Previous studies
have found increased CC size in musicians (90, 91), although it is
unclear whether this effect was solely caused by enhanced auditory
stimulation or a more integrated influence of the multisensory ex-
perience (visual, auditory, motor, and tactile) associated with intense
musical training (92). The fact that exposure to maternal sounds in
our study did not elicit significant structural changes in the CC does
not rule out the possibility that these changes would eventually
occur at a later gestational age or with longer exposure periods.
Further studies are needed to determine the degree of neural
specificity and experience-dependent plasticity induced by maternal
sounds exposure in preterm infants undergoing intensive care.
In considering the clinical relevance of our results, the limi-
tations of cranial ultrasonography should be discussed. Although
cranial ultrasound is the diagnostic imaging of choice for ruling
out the appearance of brain pathology in the population of
high-risk preterm neonates (9396), and clearly an acoustically
quieter examination than an MRI, some consider MRI to be
more accurate. Linear measurements from cranial ultrasound
have been strongly correlated with major neonatal cerebral sites
seen on MRI (72, 93, 9799), although several regions, including
the posterior horn depth of the lateral ventricle and the cortex of
the cingulate gyrus, may appear to be slightly narrower than when
measured sonographically (97). For that reason, in the present
study we intentionally chose not to focus on absolute values of
brain measurements, but rather report normalized values based on
the TTD of each infant. In the absence of MRI data available for
our cohort of newborns, this approach allowed us to reliably ex-
amine the difference in brain structures between the groups re-
gardless of whether or not the measurements correlate with MRI.
To summarize, this study provides evidence for auditory cortex
plasticity in preterm newborns receiving daily exposure to ma-
ternal sounds in the first month of life. The functional implica-
tion of this early brain plasticity is still unclear and warrants
further investigation. We theorize that exposing preterm new-
borns to mothers voice and heartbeat sounds provides them with
a biologically familiar sensory experience that may play an
important role in negating the effects of the noxious hospital
environment on brain development. In addition, the use of
recorded maternal sounds in the first month of life may be es-
pecially helpful in this high-acuity population of newborns whose
exposure to live maternal stimulation is often limited because of
infrequent parental visits. Despite the prospects of these results,
the clinical benefits of maternal sound exposure are still a matter
of speculations and no firm conclusions can be drawn based on
the present study. Clearly, preterm newborns have more working
against them than can be fully compensated for by added ex-
posure to maternal sounds. However, the present study begins
to show the effect that maternal sounds could have on very early
brain development. Further studies are needed to determine the
functional implications of these results and their predictive value
of long-term hearing and language outcomes.
Materials and Methods
Patient Population. Forty preterm newborns admitted to the NICU at Brigham
and Womens Hospital participated in this study. Newborns were randomized
to one of two groups. A description of the study population is given in Table 1.
Inclusion criteria included gestational age at birth between 25 and 32 wk and
available records of cranial ultrasounds at one month of age. Exclusion criteria
included prenatal diagnosed brain lesions, intracranial hemorrhage, cystic
periventricular leukomalacia, prominent extra-axial spaces, and dilated lateral
ventricular atria. Additional restrictive exclusion criteria were included to en-
sure our results would not be skewed by common conditions known to alter
brain anatomy, such as small for gestational age (100) and intrauterine growth
restriction (101, 102). A written informed consent was obtained from parents.
Maternal Sound Group. Newborns in the maternal sounds group (n=21) re-
ceived daily exposure to audio recordings of their mothers voice and heartbeat
sounds played inside their incubator for a total of 3 h/d (four times per day for
a duration of 45 min each). Maternal sounds were not played between midnight
and 5:00 AM and were avoided during parental visits or medical examinations.
Environmental Sound Group (Control). Control preterm newborns (n=19)
were exposed to unfiltered routine hospital noise as present in the NICU
environment with no added exposure to audio recordings of their mothers
voice and heartbeat sounds. The acoustic properties of the NICU environ-
ment were measured in a separate study. Noise measurements taken in our
NICU revealed an average higher noise levels during daytime (Leq =60.05
dBA) compared with night-time (Leq =58.67 dBA). Spectral analysis of fre-
quency bands (>50 dB) showed that infants were exposed to frequencies to
high-fervency sounds >500 Hz 57% of the time (53).
Maternal Sound Exposure. Mothers voice was recorded individually for each
infant. Voice recording was done in a standardized fashion via a large-
diaphragm condenser microphone (KSM44, Shure), capturing three types of
vocalizations (speaking, reading, and singing) from each mother. Voice re-
cordings were attenuated using a low-passfilterwithacut-offof400Hzto
mimic the low frequency womb-like experience. The mater nal v oice re-
cording was overlaid with individualized recordings of the mothers
heartbeat using a digital stethoscope (ds32a; Thinklabs Digital Stethoscopes).
This was done in an attempt to simulate the auditory experience in utero
wherein the fetus hears both the mothers voice and the sounds of her
heartbeat simultaneously. The maternal recordings were loaded onto an MP3
player (Phillips Electronics, SA2RGA04KS) for playback inside the incubator via
a micro audio system. Loud peaks >65 dBA (A-weighted) of the maternal sound
recordings were attenuated to achieve a safe level of sound delivery as was
measured by a sound level meter (Bruel & Kjaer, 2250), approximating the level
of normal human conversation (Mean LAq =58.6 dBA). The above protocol was
administered individually for each infant randomized to the maternal sounds
group as validated in a previous safety and feasibility study (103), as well as in
several experimental reports from our group (63, 104, 105).
| Webb et al.
Neonatal Cranial Ultrasound Measurements. All neonatal cranial ultrasounds
used in this study were conducted by a blinded radiology technician as part
of routine screening for neonatal brain abnormalities on day of life 30 ±3.
Post hoc measurements were obtained with electronic calipers using Cen-
tricity Enterprise Web imaging software platform (v3.0.10, GE Healthcare).
Measurements were obtained by a specially trained researcher and were
additionally verified for accuracy and reliability by an experienced radiolo-
gist specialized in neonatal cranial ultrasound reading. The group placement
of each infant remained deidentified.
The following measurements were obtained from each neonatal cranial
ultrasound. In the coronal plane: (i) thickness of the right and left AC in the
mid portion of the superior temporal gyrus, and (ii ) width of the right and
left FHs of the lateral ventricle in the short axis at the level of the foramen of
Monro. In the midsagittal plane: width of the body of the CC. The above
measurements were normalized for each infant based on the TTD (leading
edge to leading edge at the roof of the temporal horns of the lateral ven-
tricles). Sample measurements are shown in Fig. 1.
Data Analysis. SPSS 20 (IBM) was used for all data analyses. Analysis was
focused on determining the effects of sound exposure (i.e., group) on
cortical region of interest related to hearing and language. A multivariate
analysis of variance (MANOVA) was conducted to test for possible differ-
ences in the thickness of the right and left AC (dependent variables) be-
tween the groups (independent variable). An additional MANOVA was
used to compare the width of the right and left FH between the two groups.
Group differences in the width of the CC were examined with a ttest.
Spearman correlation was used to assess the association between gesta-
tional age at birth and brain measures. Within the maternal sounds group,
Spearman correlation was used to assess the association between days of
maternal sound exposure and the brain measures.
ACKNOWLEDGMENTS. We thank the families and babies who participated in
this study; Anna Alkozei and Katie Rand for their kind assistance in early stages of
this work; and Peter Forbes for statistical consultation. This study was supported
in part by grants made to A.L. from the Charles H. Hood Foundation, the Peter
and Elizabeth C. Tower Foundation, Little Giraffe Foundation, Gerber Founda-
tion, and Haileys Hope Foundation.
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| Webb et al.
... There is also the factor of timing. Early childhood represents a period of peak neural plasticity, allowing the opportunity to foster lasting and substantial effects on brain development (Fox et al., 2010;Webb et al., 2015). Infants rapidly learn through interactions with their environment. ...
Rapid advancement is paving the way to identify children who would likely benefit from early intervention during the first years of life, prior to the onset of significant delays in development. With the widely acknowledged benefits of early intervention, key questions arise: Does behavioral intervention targeted to infancy and early toddlerhood improve developmental outcomes? What procedures might be used, and under what circumstances? Who do these interventions work for? The current review comprehensively examined the literature on behavioral interventions based in operant learning paradigm, focused on key developmental areas with children in the first two years of life. We located and synthesized 45 studies with unique participant cohorts that included 1,143 children between the ages of 1 to 23 months old. Interestingly, the search revealed the majority of studies focused on infants in the first year of life, of which a large proportion investigated approaches to increase vocalizations or other forms of communication. We provide implications, limitations, and future directions on how behavioral interventions for infants and young toddlers can inform future intervention research with infant populations.
... In this Review, we will largely leave aside the mechanics of music production and perception to concentrate on the domain-specificity, development and universality of musical responses. For instance, we do not discuss cultural variation in the perception of dissonance 51 , the effects of musical experience on auditory processing 52 , or the effects of antenatal exposure on auditory perception and neural development 53,54 . Our coverage will focus on two sets of musical responses that have received considerable research attention and are among the most important psychological effects of music. ...
... It is known that music listening triggers rich brain processing comprising both cognitive and emotional neural substrates (Koelsch, 2014;Sarkamo et al., 2013;Zatorre et al., 2009). However, there is still limited knowledge regarding the effects of music interventions on the brain during early development, namely its effects on brain structure (Sa de Almeida et al., 2019;Webb et al., 2015). ...
Full-text available
Preterm birth disrupts important neurodevelopmental processes occurring from mid-fetal to term-age. Musicotherapy, by enriching infants' sensory input, might enhance brain maturation during this critical period of activity-dependent plasticity. To study the impact of music on preterm infants' brain structural changes, we recruited 54 very preterm infants randomized to receive or not a daily music intervention, that have undergone a longitudinal multi-shell diffusion MRI acquisition, before the intervention (at 33 weeks' gestational age) and after it (at term-equivalent-age). Using whole-brain fixel-based (FBA) and NODDI analysis (n = 40), we showed a longitudinal increase of fiber cross-section (FC) and fiber density (FD) in all major cerebral white matter fibers. Regarding cortical grey matter, FD decreased while FC and orientation dispersion index (ODI) increased, reflecting intracortical multidirectional complexification and intracortical myelination. The music intervention resulted in a significantly higher longitudinal increase of FC and ODI in cortical paralimbic regions, namely the insulo-orbito-temporopolar complex, precuneus/posterior cingulate gyrus, as well as the auditory association cortex. Our results support a longitudinal early brain macro and microstructural maturation of white and cortical grey matter in preterm infants. The music intervention led to an increased intracortical complexity in regions important for socio-emotional development, known to be impaired in preterm infants.
... There is an existential story as a mother's heartbeat makes her newborn baby relax. Although to the best of our knowledge, there has not been a line of studies that consolidated this story, one study reported that the mother's heartbeat contributes to the development of the brain of newborns [11]. In addition to this study, the possible interactions between music and heartbeat have been demonstrated earlier. ...
The heartbeat music interaction has been conceivable, but it is not been scientifically pursued yet. In this study, we developed a heartrate music feedback architecture where the tempo of the music track was continuously changed in accordance with users’ heart rate in a real-time manner and conducted a preliminary experiment to explore its psychophysiological effect in a laboratory setting. Compared with the control condition, in which the tempo of the music tracks was constant, there were significant differences among conditions in the respiration intervals, heart rate variability, and the beta power of brain waves. Furthermore, there was no distinct difference in the subjective scores and impressions for the musical tracks. The results imply that the difference in the physiological responses between the conditions may be derived not from perceptible or recognizable differences in music, but from purely physiological functioning at unconscious level.
... Another study conducted on premature infants examined the effect of sound intervention until the infants reached term using cranial ultrasonography. The results showed that the degree of the right and left auditory cortex development was not significantly correlated with the duration of music exposure [50]. ...
Full-text available
Background The developing nervous system in utero is exposed to various stimuli with effects that may be carried forward to the neonatal period. This study aims to investigate the effects of sound stimulation (music and speech) on fetal memory and learning, which was assessed later in neonatal period. Methods The MEDLINE (pubmed), Scopus, EMBASE, and Cochrane Library were searched. Two reviewers selected the studies and extracted the data independently. The quality of eligible studies was assessed using The Joanna Briggs Institute Critical Appraisal Checklist for Randomized Controlled Trials (RCTs). Results Overall 3930 articles were retrieved and eight studies met the inclusion criteria. All of the included studies had good general quality; however, high risk of selection and detection bias was detected in most of them. Fetal learning was examined through neonatal electrocardiography (ECG), electroencephalography (EEG), habituation tests, and behavioral responses. Seven studies showed that the infants had learned the fetal sound stimulus and one study indicated that the prenatally stimulated infants performed significantly better on a neonatal behavior test. There was considerable diversity among studies in terms of sound stimulation type, characteristics (intensity and frequency), and duration, as well as outcome assessment methods. Conclusions Prenatal sound stimulation including music and speech can form stimulus-specific memory traces during fetal period and effect neonatal neural system. Further studies with precisely designed methodologies that follow safety recommendations, are needed. Graphical Abstract
... The previous 1995-2015 review identified evidence-based auditory exposures to be live music/singing [65,66], recorded music/ singing/maternal voice [67][68][69][70][71], and recorded maternal biological sounds [72,73]. This new 2015-2020 integrative review added an additional 9 articles, representing 6 different cohorts, on auditory interventions. ...
Full-text available
To inform changes to the Supporting and Enhancing NICU Sensory Experiences (SENSE) program, studies investigating sensory-based interventions in the NICU with preterm infants born ≤32 weeks were identified. Studies published between October 2015 to December 2020, and with outcomes related to infant development or parent well-being, were included in this integrative review. The systematic search used databases including MEDLINE, Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, and Google Scholar. Fifty-seven articles (15 tactile, 9 auditory, 5 visual, 1 gustatory/olfactory, 5 kinesthetic, and 22 multimodal) were identified. The majority of the sensory interventions that were identified within the articles were reported in a previous integrative review (1995-2015) and already included in the SENSE program. New evidence has led to refinements of the SENSE program, notably the addition of position changes across postmenstrual age (PMA) and visual tracking starting at 34 weeks PMA.
... As early as 25 weeks gestational age hearing is functional (Eggermont and Moore, 2012), and structural components of the auditory system allow the fetus to hear the omnipresent rhythmic sounds of the maternal heartbeat and respiration as well environmental rhythms (Parncutt, 2016). The prenatal experience with different forms of rhythmic stimulation (both intra-and extra-uterine) influences the maturation of neural circuits that later support rhythm development (Webb et al., 2015), and hence later rhythmic capacities. Neural evidence suggests late premature and full-term newborns are already sensitive to rhythmic temporal patterns (Edalati et al., 2022;Háden et al., 2015;Winkler et al., 2009), and behavioral evidence suggests that newborns use rhythm to discriminate between language categories (Nazzi et al., 1998;Ramus et al., 2000). ...
Full-text available
Studies of rhythm processing and of reward have progressed separately, with little connection between the two. However, consistent links between rhythm and reward are beginning to surface, with research suggesting that synchronization to rhythm is rewarding, and that this rewarding element may in turn also boost this synchronization. The current mini review shows that the combined study of rhythm and reward can be beneficial to better understand their independent and combined roles across two central aspects of cognition: 1) learning and memory, and 2) social connection and interpersonal synchronization; which have so far been studied largely independently. From this basis, it is discussed how connections between rhythm and reward can be applied to learning and memory and social connection across different populations, taking into account individual differences, clinical populations, human development, and animal research. Future research will need to consider the rewarding nature of rhythm, and that rhythm can in turn boost reward, potentially enhancing other cognitive and social processes.
The formation of myelin, the fatty sheath that insulates nerve fibers, is critical for healthy brain function. A fundamental open question is what impact being born has on myelin growth. To address this, we evaluated a large ( n = 300) cross-sectional sample of newborns from the Developing Human Connectome Project (dHCP). First, we developed software for the automated identification of 20 white matter bundles in individual newborns that is well suited for large samples. Next, we fit linear models that quantify how T1w/T2w (a myelin-sensitive imaging contrast) changes over time at each point along the bundles. We found faster growth of T1w/T2w along the lengths of all bundles before birth than right after birth. Further, in a separate longitudinal sample of preterm infants ( N = 34), we found lower T1w/T2w than in full-term peers measured at the same age. By applying the linear models fit on the cross-section sample to the longitudinal sample of preterm infants, we find that their delay in T1w/T2w growth is well explained by the amount of time they spent developing in utero and ex utero. These results suggest that white matter myelinates faster in utero than ex utero. The reduced rate of myelin growth after birth, in turn, explains lower myelin content in individuals born preterm and could account for long-term cognitive, neurological, and developmental consequences of preterm birth. We hypothesize that closely matching the environment of infants born preterm to what they would have experienced in the womb may reduce delays in myelin growth and hence improve developmental outcomes.
Full-text available
Objective: We designed and implemented a novel neonatal intensive care (NICU) lighting system to support current understanding of sunlight-coupled physiology. Methods: We created a system that generates wavelengths corresponding to the known blue and violet activation spectra of non-visual opsins. These are known to mediate energy management and related physiologic activity. Results: Light produced by the system spans the visible spectrum, including violet wavelengths that are blocked by modern glazing and not emitted by standard LED fixtures. System features include automated light and dark phases that mimic dawn/dusk. The system also matches length of day seasonality. Spectral composition can be varied to support translational research protocols. Implementation required a comprehensive strategy to inform bedside providers about the value and use of the lighting system. Conclusion: Full-spectrum lighting for the NICU is feasible and will inform optimization of the NICU environment of care to support optimal neonatal growth and development.
Full-text available
Using in-vivo magnetic resonance morphometry it was investigated whether the midsagittal area of the corpus callosum (CC) would differ between 30 professional musicians and 30 age-, sex- and handedness-matched controls. Our analyses revealed that the anterior half of the CC was significantly larger in musicians. This difference was due to the larger anterior CC in the subgroup of musicians who had begun musical training before the age of 7. Since anatomic studies have provided evidence for a positive correlation between midsagittal callosal size and the number of fibers crossing through the CC, these data indicate a difference in interhemispheric communication and possibly in hemispheric (a)symmetry of sensorimotor areas. Our results are also compatible with plastic changes of components of the CC during a maturation period within the first decade of human life, similar to those observed in animal studies.
Full-text available
In humans, the most obvious functional lateralization is the specialization of the left hemisphere for language. Therefore, the involvement of the right hemisphere in language is one of the most remarkable findings during the last two decades of fMRI research. However, the importance of this finding continues to be underestimated. We examined the interaction between the two hemispheres and also the role of the right hemisphere in language. From two seeds representing Broca's area, we conducted a seed correlation analysis (SCA) of resting state fMRI data and could identify a resting state network (RSN) overlapping to significant extent with a language network that was generated by an automated meta-analysis tool. To elucidate the relationship between the clusters of this RSN, we then performed graph theoretical analyses (GTA) using the same resting state dataset. We show that the right hemisphere is clearly involved in language. A modularity analysis revealed that the interaction between the two hemispheres is mediated by three partitions: A bilateral frontal partition consists of nodes representing the classical left sided language regions as well as two right-sided homologs. The second bilateral partition consists of nodes from the right frontal, the left inferior parietal cortex as well as of two nodes within the posterior cerebellum. The third partition is also bilateral and comprises five regions from the posterior midline parts of the brain to the temporal and frontal cortex, two of the nodes are prominent default mode nodes. The involvement of this last partition in a language relevant function is a novel finding.
Using in-vivo magnetic resonance morphometry it was investigated whether the midsagittal area of the corpus callosum (CC) would differ between 30 professional musicians and 30 age-, sex- and handedness-matched controls. Our analyses revealed that the anterior half of the CC was significantly larger in musicians. This difference was due to the larger anterior CC in the subgroup of musicians who had begun musical training before the age of 7. Since anatomic studies have provided evidence for a positive correlation between midsagittal callosal size and the number of fibers crossing through the CC, these data indicate a difference in interhemispheric communication and possibly in hemispheric (a)symmetry of sensorimotor areas. Our results are also compatible with plastic changes of components of the CC during a maturation period within the first decade of human life, similar to those observed in animal studies.
Nature Reviews Neuroscience 10, 647–658 (2009) On page 654 of the above article, the scale bar in parts a and f of figure 4 should represent 5 μm rather than 5 mm. This has been corrected in the online version.
Using high-resolution in vivo magnetic resonance morphometry we measured forebrain volume (FBV), midsagittal size of the corpus callosum (CC) and four CC subareas in 120 young and healthy adults (49 women, 71 men). We found moderate linear and quadratic correlations, indicating that the CC and all CC subareas increase with FBV both in men and women (multiple r 2 ranging from 0.10 to 0.28). Allometric equations revealed that these increases were less than proportional to FBV (r 2 ranging from 0.02 to 0.30). Absolute CC measurements, as well as CC subareas relative to total CC or FBV (the latter measures termed the CC ratios), were further analyzed with regard to possible effects of handedness, gender, or handedness by gender interaction. Contrary to previous reports, left-handers did not show larger CC measurements compared to right-handers. The only apparent influence of gender was on the CC ratios, which were larger in women. However, smaller brains had larger CC ratios which were mainly independent of gender, a result of the less than proportional increase of callosal size with FBV. We suggest that the previously described gender differences in CC anatomy may be better explained by an underlying effect of brain size, with larger brains having relatively smaller callosa. This lends empirical support to the hypothesis that brain size may be an important factor influencing interhemispheric connectivity and lateralization.
AimRecent research raises concerns about the adverse effects of noise exposure on the developing preterm infant. However, current guidelines for NICU noise remain focused on loudness levels, leaving the problem of exposure to potentially harmful sound frequencies largely overlooked. This study examined the frequency spectra present in a level-II NICU.Methods Noise measurements were taken in two level-II open-bay nurseries. Measurements were taken over five days for a period of 24 hours each. Spectral analysis was focused on comparing sound frequencies in human speech range during daytime (7AM-7PM) vs. nighttime (7PM-7AM).ResultsOn average, daytime noise levels (Leq = 60.05 dBA) were higher than nighttime (Leq = 58.67 dBA). Spectral analysis of frequency bands (>50 dB) revealed that infants were exposed to frequencies <500 Hz 100% of the time, and to frequencies >500 Hz 57% of the time. During daytime, infants were exposed to nearly 20% more sounds within the speech frequency range compared to nighttime (p=.018).Conclusion Measuring the frequency spectra of NICU sounds is necessary to attain a thorough understanding of both the noise levels and the type of sounds that preterm infants are exposed to throughout their hospital stay. The risk of high-frequency noise exposure in the preterm population is still unclear and warrants further investigation.This article is protected by copyright. All rights reserved.
To evaluate brain development longitudinally in premature infants without abnormalities as compared to healthy full-term newborns, we assessed fMRI brain activity patterns in response to linguistic stimuli and white matter structural development focusing on language-related fibres. A total sample of 29 preterm newborns and 26 at term control newborns underwent both fMRI and DTI. Griffiths test was performed at 6 months of corrected age to assess development. Auditory fMRI data were analysed in 17 preterm newborns at three time points [34, 41 and 44 weeks of post menstrual age (wPMA)] and in 15 controls, at term. Analysis showed a distinctive pattern of cortical activation in preterm newborns up to 29 wPMA moving from early prevalent left temporal and supramarginal area activation in the preterm period, to a bilateral temporal and frontoopercular activation in the at term equivalent period and to a more fine-grained left pattern of activity at 44 wPMA. At term controls showed instead greater bilateral posterior thalamic activation. The different pattern of brain activity associated to preterm newborns mirrors their white matter maturation delay in peripheral regions of the fibres and thalamo-cortical radiations in subcortical areas of both hemispheres, pointing to different transient thalamo-cortical development due to prematurity. Evidence for functional thalamic activation and more mature subcortical tracts, including thalamic radiations, may represent the substantial gap between preterm and at term infants. The transition between bilateral temporal activations at term age and leftward activations at 44 weeks of PMA is correlated to better neuropsychological results in Griffiths test.
Purpose: The purpose of this study was to evaluate the effect of low-pass filtering on the detection of word-final /s/ and /z/ for children and adults with normal hearing. Method: Stimuli were nouns from the University of Western Ontario Plurals Test (Glista & Scollie, 2012), low-pass filtered with 5 different cutoff frequencies: 8000 Hz, 5000 Hz, 4000 Hz, 3000 Hz, and 2000 Hz. Listeners were children (age range = 7-13 years) and adults with normal hearing. The task was a 2-alternative forced-choice task with a picture-pointing response. Results: Performance was worse for lower than for higher low-pass filter cutoff frequencies, but the effect of low-pass filtering was similar for children and adults. Nearly all listeners achieved 100% correct performance when stimuli were low-pass filtered with cutoff frequencies of 8000 Hz or 5000 Hz. Performance remained well above chance even for the most severe filtering condition (2000 Hz). Restricting high-frequency audibility influenced performance for plural items to a greater extent than for singular items. Conclusion: The results indicate that children and adults with normal hearing can use acoustic information below the spectral range of frication noise typically associated with /s/ and /z/ to discriminate between singular and plural forms of nouns in the context of the University of Western Ontario Plurals Test.
Cranial ultrasonography (cUS) is a reliable tool to detect the most frequently occurring congenital and acquired brain abnormalities in full-term and preterm neonates. Appropriate equipment, including a dedicated ultrasound machine and appropriately sized transducers with special settings for cUS of the newborn brain, and ample experience of the ultrasonographist are required to obtain optimal image quality. When, in addition, supplemental acoustic windows are used whenever indicated and cUS imaging is performed from admission throughout the neonatal period, the majority of the lesions will be diagnosed with information on timing and evolution of brain injury and on ongoing brain maturation. For exact determination of site and extent of lesions, for detection of lesions that (largely or partially) remain beyond the scope of cUS and for depiction of myelination, a single, well timed MRI examination is invaluable in many high risk neonates. However, as cUS enables bedside, serial imaging it should be used as the primary brain imaging modality in high risk neonates.