How does sound shapes the minds of fetuses in the womb ?


Scientists have yet to answer the age-old question of whether or how sound shapes the minds of fetuses in the womb, and expectant mothers often wonder about the benefits of such activities as playing music during pregnancy.

Now, in experiments in newborn mice, scientists at Johns Hopkins report that sounds appear to change “wiring” patterns in areas of the brain that process sound earlier than scientists assumed and even before the ear canal opens.

The current experiments involve newborn mice, which have ear canals that open 11 days after birth. In human fetuses, the ear canal opens prenatally, at about 20 weeks gestation.

The findings, published online Feb. 12 in Science Advances, may eventually help scientists identify ways to detect and intervene in abnormal wiring in the brain that may cause hearing or other sensory problems.

“As scientists, we are looking for answers to basic questions about how we become who we are,” says Patrick Kanold, Ph.D., professor of biomedical engineering at The Johns Hopkins University and School of Medicine. “Specifically, I am looking at how our sensory environment shapes us and how early in fetal development this starts happening.”

Kanold started his career in electrical engineering, working with microprocessors, a natural conduit for his shift to science and studying the circuitry of the brain.

His research focus is the outermost part of the brain, the cortex, which is responsible for many functions, including sensory perception. Below the cortex is the white brain matter that in adults contains connections between neurons.

In development, the white matter also contains so-called subplate neurons, some of the first to develop in the brain – at about 12 weeks gestation for humans and the second embryonic week in mice. Anatomist Mark Molliver of Johns Hopkins is credited with describing some of the first connections between neurons formed in white matter, and he coined the term subplate neurons in 1973.

These primordial subplate neurons eventually die off during development in mammals, including mice. In humans, this happens shortly before birth through the first few months of life. But before they die off, they make connections between a key gateway in the brain for all sensory information, the thalamus, and the middle layers of the cortex.

“The thalamus is the intermediary of information from the eyes, ears and skin into the cortex,” says Kanold.

“When things go wrong in the thalamus or its connections with the cortex, neurodevelopmental problems occur.” In adults, the neurons in the thalamus stretch out and project long, armlike structures called axons to the middle layers of the cortex, but in fetal development, subplate neurons sit between the thalamus and cortex, acting as a bridge.

At the end of the axons is a nexus for communication between neurons called synapses.

Working in ferrets and mice, Kanold previously mapped the circuitry of subplate neurons. Kanold also previously found that subplate neurons can receive electrical signals related to sound before any other cortical neurons did.

The current research, which Kanold began at his previous position at the University of Maryland, addresses two questions, he says: When sound signals get to the subplate neurons, does anything happen, and can a change in sound signals change the brain circuits at these young ages?

First, the scientists used genetically engineered mice that lack a protein on hair cells in the inner ear. The protein is integral for transforming sound into an electric pulse that goes to the brain; from there it is translated into our perception of sound. Without the protein, the brain does not get the signal.

In the deaf, 1-week-old mice, the researchers saw about 25% – 30% more connections among subplate neurons and other cortex neurons, compared with 1-week-old mice with normal hearing and raised in a normal environment.

This suggests that sounds can change brain circuits at a very young age, says Kanold.

In addition, say the researchers, these changes in neural connections were happening about a week earlier than typically seen. Scientists had previously assumed that sensory experience can only alter cortical circuits after neurons in the thalamus reach out to and activate the middle layers of the cortex, which in mice is around the time when their ear canals open (at around 11 days).

When neurons are deprived of input, such as sound, the neurons reach out to find other neurons, possibly to compensate for the lack of sound,” says Kanold. “This is happening a week earlier than we thought it would, and tells us that the lack of sound likely reorganizes connections in the immature cortex.”

In the same way that lack of sound influences brain connections, the scientists thought it was possible that extra sounds could influence early neuron connections in normal hearing mice, as well.

To test this, the scientists put normal hearing, 2-day-old mouse pups in a quiet enclosure with a speaker that sounds a beep or in a quiet enclosure without a speaker. The scientists found that the mouse pups in the quiet enclosure without the beeping sound had stronger connections between subplate and cortical neurons than in the enclosure with the beeping sound.

However, the difference between the mice housed in the beeping and quiet enclosures was not as large as between the deaf mice and ones raised in a normal sound environment.

These mice also had more diversity among the types of neural circuits that developed between the subplate and cortical neurons, compared with normal hearing mouse pups raised in a quiet enclosure with no sound. The normal hearing mice raised in the quiet enclosure also had neuron connectivity in the subplate and cortex regions similar to that of the genetically-engineered deaf mice.

“In these mice we see that the difference in early sound experience leaves a trace in the brain, and this exposure to sound may be important for neurodevelopment,” says Kanold.

The research team is planning additional studies to determine how early exposure to sound impacts the brain later in development. Ultimately, they hope to understand how sound exposure in the womb may be important in human development and how to account for these circuit changes when fitting cochlear implants in children born deaf. They also plan to study brain signatures of premature infants and develop biomarkers for problems involving miswiring of subplate neurons.

increasingly interested in fetal perception and cognition. In a cross-cultural survey of maternal knowledge and beliefs concerning fetal development conducted in France and Canada, investigators (Kisilevsky, Beti, Hains & Lecanuet, 2001) found that many mothers-to-be believe that all perceptual systems are developed by about 25 weeks gestational age (GA).

The majority of the re- spondents also believe that fetuses react to music about 1 week later and about half believe that fetuses have emotions and thoughts. Moreover, there is a common belief that playing music to fetuses and infants increases intelligence.

The evidence for a positive effect of music on infant development is mostly anecdotal and is perhaps reinforced by a plethora of commercial audio-recordings (e.g. music, heart sounds) and devices purported to enrich the fetal environment and increase infant IQ.
Although it is difficult to find any scientific evidence for the ‘music for a better brain’ claim, Gray et al. (2001) argue that there is a biological and evolutionary origin of musical ability, and according to Tramo (2001), all of us are born with the capacity to apprehend emotion and meaning in music.

If so, then this capacity should be present in near-term fetuses. We know that fetuses can hear by the last trimester of pregnancy (e.g. Kisilevsky,Pang & Hains, 2000) and that music played in the external environment is recognizable in utero (Querleu, Renard, Boutteville & Crepin, 1989).

There is some evidence that term fetuses can distinguish between voices (mother versus stranger, Kisilevsky et al., 2003; male versus female, Lecanuet et al., 1993) and musical notes (piano D4 versus C5, Lecanuet, Granier-Deferre, Jacquet & DeCasper, 2000) as well as habituate to a brief piano sequence with changing melodic contour (Granier-Deferre, Bassereau, Jacquet & Lecanuet, 1998).

While there has been very little work in the area of fetal perception of music per se, fetal auditory percep- tion is well described. By about 30 weeks GA, fetuses begin to respond to brief episodes (2–3 seconds) of relat- ively loud (110 dB sound pressure level [SPL]) airborne sounds with heart rate acceleration and body movement responses (Kisilevsky et al., 2000).

As gestation advances, the frequency and magnitude of responses increases and the threshold for a response decreases. At term, the com- plexity of the stimulus (pure tone, white noise, speech) as well as its intensity and frequency regulate the threshold and magnitude of a response (see Lecanuet, Granier- Deferre & Busnel, 1995 and reviews by Lecanuet & Schaal, 1996 and Kisilevsky & Low, 1998). Clearly, by late gestation the fetus can hear, and fetal auditory perceptual abilities become more sensitive with the maturation of the auditory system.

The studies on the development of fetal hearing have used brief bursts of noise emitted over seconds rather than prolonged noise over a period of time as would be more typical of environmental sounds such as music. However, some previous studies have examined the effects of music on fetal behaviour using longer episodes of stimulation. Sontag, Steele & Lewis (1969) played a 10-minute tape-recorded passage of the mother’s favourite piece of music through two floor speakers placed at the foot of a bed; intensity averaged 75 dB (range 65 dB to 100 dB) measured at the mother’s head.

In fetuses from 28 weeks GA to term (n 11), they found that a significant cardiac acceleration (about 5 beats per minute) occurred 90 seconds after music onset. There were no changes in fetal body movements and no change in maternal heart rate.

Fetal heart rate returned to baseline within 2 minutes of music onset. Because the onset of the response was delayed and there was no change in activity, the authors speculated that fetal response was mediated through the emotional reaction of the mother.

Similarly, Zimmer et al. (1982) posited that changes in fetal behaviour were mediated by maternal hormonal changes when they played music via headphones to pregnant women at 34 – 40 weeks gestation (i.e. masked to the fetus). They found that fetuses showed decreased breathing activity and increased body movements if the mother listened to a preferred type of music (classical versus rock).

Other early attempts to characterize the effects of music on fetal behaviour were unsuccessful. Olds (1985a, 1985b) played various classical music pieces to fetuses from 30 weeks GA via headphones placed on the maternal abdomen. He noted that variability in fetal heart rate occurred during the music.

However, fetal responses were not uniform, with heart rate increasing for some and decreasing for others, and statistical tests were not reported. It may be that Olds’ fetal results were con- founded by maternal responses, for Olds did not mask the music to the mother so that fetal behaviour could have been influenced by maternal emotional response.

While the results of Olds’ work are equivocal, Hepper (1991) demonstrated limited fetal and newborn response to music in a series of studies examining learning before and after birth. For fetuses and newborns the procedure was similar: a no-music baseline period followed by a 3- minute music period with statistical comparisons between either a 30-second baseline and the last 30 seconds of the music period (newborns) or a 1-minute baseline and the last minute of the music period (fetuses).

An increase in body movements was elicited by the theme song of a television soap opera in a group of 36 –37 weeks GA fetuses whose mothers had watched the programme throughout their pregnancies, but not in a group of

younger fetuses, 29 –30 weeks GA, or a group whose mothers had not watched the programme. Two- to 4- day-old newborns showed the opposite response, a decrease in movement and heart rate and the adoption of an alert state.

However, they showed no change in behaviour when the theme song was played backwards or when a theme song of a programme their mother had not watched during pregnancy was played. At 21 days of age, infants whose mothers had not watched the programme since delivery showed no response to the theme tune.

Taken together, these findings indicate that fetal response to a particular piece of music is experience- dependent, and experience with the music must be con- tinued after birth for the response to continue.

The results of studies examining the effects of music on newborns and premature infants could indicate the capabilities of fetuses of equivalent GA. Findings from studies of the development of active cochlear mechanisms in premature infants demonstrate that otoacoustic emissions (OAE) indicating outer hair cell activity begin at about 30 weeks conceptual age (Morlet et al., 1995) with functional maturation nearly complete by 33 weeks (Morlet, Collet, Salle & Morgon, 1993).

A lack of activity in the medial olivocochlear system indicates functional immaturity in the auditory pathway relaying information to the cortex (Morlet et al., 1993). Thus, it is unlikely that fetuses of less than 33 weeks GA are capable of the higher order processing necessary for complex auditory stimuli and music in particular. Nevertheless, music has been shown to have positive effects on premature infant behaviour.

From 31 weeks GA, premature infant behavi- ours (i.e. heart rate, state-of-arousal, facial expressions of pain) returned to baseline more rapidly when Brahms’ Lullaby (vocal or piano) was played immediately following heel lance (Butt & Kisilevsky, 2000) than in a no-music comparison condition.

The results of non-contingent music in the premature nursery environment are equivo- cal. Playing 10 minutes of non-contingent music in the isolette, Lorch, Lorch, Diefendorf and Earl (1994) found that premature infants were excited (increased heart rate) or quieted (decreased heart rate) by different music pieces.

In contrast, when female vocalist recordings of lullabies were delivered via headphones for 20 minutes over three consecutive days, Standley and Moore (1995) found that oxygen saturation increased during music on day 1 only and decreased in the post-music period on days 2 and 3.

While the outcome of playing non-contingent music in the premature nursery is equivocal, Kaminski and Hall (1996) suggest that it is beneficial in the normal newborn nursery (i.e. full-term infants). During a 6- hour observation, including both a no-music and a music period, they found fewer high arousal states and fewer state changes during music compared to no-music.

Kaminski and Hall chose Brahms’ Lullaby for their study because the tempo approximated the rate of the maternal heartbeat, 65 – 80 beats per minute, which DeCasper and Sigafoos (1983) had shown to be an effect- ive reinforcer for infants in an operant learning task, presumably because of their previous experience.

DeCasper and Carstens (1981) also found that newborns modulate their sucking to elicit music if they have had prior contingent experience with it (i.e. previous experience with producing vocal music by increasing the inter-burst interval of non-nutritive sucking) but not if the experience was non-contingent.

Although music has a number of characteristics that affect adult response (e.g. pitch, rhythm, tempo; Parsons, 2001), little is known about how they affect fetal re- sponses. Lecanuet and colleagues have demonstrated that fetuses can discriminate two low-pitched musical notes (Lecanuet et al., 2000) and two different tempi (Lecanuet, unpublished data).

In older infants, a higher pitch is more effective in capturing and holding atten- tion (Trainor & Zacharias, 1998) while variations in tempo can excite (fast) or soothe (slow) (Trehub, Hill & Kamenetsky, 1997).
In summary, while it appears that near-term fetuses respond to a music stimulus which has been repeatedly presented in the environment and that fetuses can discriminate some characteristics of music (e.g. notes, tempi) that affect adult responses, no studies have systematically examined fetal perception of a music stimulus over gestational age.

Thus, third trimester development of auditory perception using a music stimulus will be exam- ined in the present study as well as the effects of variations in tempo on fetal behaviour. For this first step in characterizing the maturation of fetal perception of a music stimulus, we chose to use Brahms’ Lullaby because of its successful use with premature and full-term infants as noted above.

In this study, we demonstrated a maturation of music perception over the last trimester of pregnancy using both movement and heart rate measures. Body move- ment responses were not observed until 35 weeks GA, when both the number of fetuses showing body move- ments and the duration of the movements increased to a maximum after about 3 minutes of stimulation.

These findings are similar to those of Hepper (1991). In his fetal learning study, he demonstrated an increase in body movements over baseline at 3 minutes after the onset of a familiar piece of music for near-term fetuses, 36 –37 weeks GA, but not for a group of younger fetuses, 29 – 30 weeks GA, or for fetuses to whom the music was not familiar.

What is clear from these two studies is that near-term fetuses can show an increase in body move- ments when hearing music; the specific aspect of music eliciting the increase in movements or learned by the fetus is unknown at this time.

Fetuses in all age groups (28 weeks GA to term) showed some heart rate response to the music stimulus, summarized in Table 2. The maturation of cardiac response was shown by changes in the direction of the response as a function of fetal age and sound intensity.

Over the first 30 seconds, music at the highest sound level generally elicited a heart rate acceleration (thought to indicate arousal) while lower intensities elicited a deceleration until by term all of the sound levels tested elicited a deceleration at music onset (thought to indicate attention).

Over the course of the 5-minute music period, fetuses from 33 to 37 weeks GA showed a gradual heart rate acceleration that did not differ over sound levels. The term fetuses showed an increase in heart rate to the faster tempo, whereas the lullaby played at the normal tempo had little effect on heart rate. Both Sontag et al. (1969) and Kisilevsky et al. (2003) examined fetal heart rate response to continuous, prolonged airborne sounds using music and voice stimuli respectively.

In Sontag’s music study, fetuses of varying ages responded with a heart rate acceleration within two minutes of music onset played at an average of 75 dB SPL. In the voice study, term fetuses responded with an increase in heart rate over a 2-minute period to their mothers’ voices and a similar decrease to a stranger’s voice, both delivered at 95 dB. The sustained heart rate acceleration response to music observed in the previous study and in this study, as well as to the mothers’ voices (Kisilevsky et al., 2003), may represent the influence of experience.

In adults, auditory experience changes the make-up of areas in the cerebral cortex that are involved in the processing of complex sounds, including music, and the changes in auditory cortical representations are based on activity-dependent modifications of synaptic circuitry (Rauschecker, 2001). However, fetal music response is probably not cortical in origin as, at this time, mature axons are present only in the most superficial layer of the cortex (Moore, 2002). However, processing of musical elements such as frequency (e.g. Giraud et al., 2000) and pitch (e.g. Braun, 2000) probably occurs in the inferior colliculus in adults, so that it is possible that the fetal behaviour observed here signifies the onset of these abilities.

The maturational changes observed here may reflect maturation of the peripheral auditory system and physiological development of the different brainstem auditory nuclei that will transmit basilar coding up to the inferior colliculi (Frisina, 2001). The neural basis of hearing begins with maturation of cochlear hair cells over early to mid-gestation (e.g. Pujol, Lavigne-Rebillard & Uziel, 1991; Rubel & Fritzsch, 2002). Beyond the cochlea, there is a complexity of overlapping cell layers in the pathways leading to the auditory cortex. In the brain stem, path length increases (Moore et al., 1996) and axonal conduction time reaches maturity by 40 weeks GA (Ponton, Moore & Eggermont, 1996).

The effect of tempo on the responses of the term fetuses can be explained in terms of arousal. A faster tempo gives rise to more activation of the cochlea and auditory fibres, so that the differential response to tempo by term fetuses might reflect a difference in arousal levels as a result of more stimulation of the reticular formation.

Alternatively, it may provide evidence that tempo is a salient stimulus for term fetuses, suggesting continuity in pre- and post-natal music perception. If the assump- tion is made that there is continuity from fetus to new- born, then it is also feasible that changes in the direction of the fetal heart rate response over late gestation rep- resent a change in processing from simple discrimination of the signal to attention, reflecting primitive cognitive function.

Continuity of responding before and after birth has been demonstrated previously with brief duration (2.5 seconds) sound and vibration (e.g. Kisilevsky & Muir, 1991) and with short musical melodies (Granier-Deferre et al., 1998). Finding a systematic change in fetal heart rate following the onset of the music suggests that the fetuses were aware that the music was different from the ongoing background uterine sounds that have a rhythmic quality (e.g. discriminating the music from the maternal heart rate) or that the music masks these back- ground sounds.

In summary, our findings add to the small body of knowledge concerning fetal cognitive abilities. Although it is difficult to demonstrate the same abilities in the fetus that have been demonstrated with newborns, this study has explored the time course of the origins of these abilities. It seems that near-term fetuses are able to make simple discriminations (i.e. renew responding or respond differently to a change in stimulus parameter) based on a number of dimensions (e.g. tempo, reported here; loud- ness and pitch, Lecanuet et al., 2000), and have some rudimentary memory of music (Hepper, 1991) and short speech sequences (i.e. child’s rhyme, DeCasper et al., 1994). ùAlso, not only can they distinguish between some complex auditory stimuli (voices) but also respond differ- entially to variations. Our findings characterize the mat- uration of responding to a complex auditory stimulus and provide evidence that higher order auditory percep- tion begins before birth.

reference link:

More information: Early peripheral activity alters nascent subplate circuits in the auditory cortex, Science Advances (2021). DOI: 10.1126/sciadv.abc9155 , … .1126/sciadv.abc9155


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