Newborn's neural representation of instrumental and vocal music as revealed by fMRI: A dynamic effective brain connectivity study.

Music is ubiquitous, both in its instrumental and vocal forms. While speech perception at birth has been at the core of an extensive corpus of research, the origins of the ability to discriminate instrumental or vocal melodies is still not well investigated. In previous studies comparing vocal and musical perception, the vocal stimuli were mainly related to speaking, including language, and not to the non-language singing voice. In the present study, to better compare a melodic instrumental line with the voice, we used singing as a comparison stimulus, to reduce the dissimilarities between the two stimuli as much as possible, separating language perception from vocal musical perception. In the present study, 45 newborns were scanned, 10 full-term born infants and 35 preterm infants at term-equivalent age (mean gestational age at test = 40.17 weeks, SD = 0.44) using functional magnetic resonance imaging while listening to five melodies played by a musical instrument (flute) or sung by a female voice. To examine the dynamic task-based effective connectivity, we employed a psychophysiological interaction of co-activation patterns (PPI-CAPs) analysis, using the auditory cortices as seed region, to investigate moment-to-moment changes in task-driven modulation of cortical activity during an fMRI task. Our findings reveal condition-specific, dynamically occurring patterns of co-activation (PPI-CAPs). During the vocal condition, the auditory cortex co-activates with the sensorimotor and salience networks, while during the instrumental condition, it co-activates with the visual cortex and the superior frontal cortex. Our results show that the vocal stimulus elicits sensorimotor aspects of the auditory perception and is processed as a more salient stimulus while the instrumental condition activated higher-order cognitive and visuo-spatial networks. Common neural signatures for both auditory stimuli were found in the precuneus and posterior cingulate gyrus. Finally, this study adds knowledge on the dynamic brain connectivity underlying the newborns capability of early and specialized auditory processing, highlighting the relevance of dynamic approaches to study brain function in newborn populations.

Maternal singing sustains preterm hospitalized newborns' autonomic nervous system maturation: an RCT.

BACKGROUND: Premature birth is known to affect the newborn's autonomic nervous system (ANS) maturation, with potential short and long-term impact on their neurobehavioral development. The purpose of the study was to investigate the effects of maternal directed singing and speaking on the preterm infants' autonomic nervous system (ANS) maturation as measured by the heart rate variability (HRV) parameters. METHODS: In this multi-center randomized clinical trial, 30 stable preterm infants (m = 29,6 weeks of gestational age), without any abnormalities were randomized into an intervention (16) or a control group (14). HRV was measured weekly, for a total of 80 recordings during hospitalization, as well as before and after each session of singing or speaking. RESULTS: The intervention group showed a significant increase of the percentage value of HRV power in the high frequency range when compared to the control group (p = 0.044). More specifically, the maternal singing significantly increased the high frequency power and decreased the low/high frequency power ratio (p = 0.037). CONCLUSIONS: The preterm infant's vagal activity significantly increased in the intervention group, potentially enhancing their ANS maturation. The effect is specifically evidenced in the singing condition. IMPACT: Maternal singing affects the autonomic nervous system maturation of preterm hospitalized newborns in the NICU. No previous studies investigated how early vocal parental intervention can affect preterm infants developement, throught their autonomic nervous system maturation. Early Vocal Contact as an early intervention involving parents has a positive impact on preterm infant's development and it can be easily implemented in the care of preterm infants. TRIAL REGISTRATION: NCT04759573, retrospectively registered, 17 February 2021.

Maternal singing reduced pain indexes in 2-month-old infants and increased proximity during vaccinations.

AIM: Immunisation is a global health priority, but methods of non-pharmacological pain relief are not widely used in routine clinical practice. In this study, we set out to investigate the effects of maternal singing during the routine vaccination of infants. METHODS: We recruited 67 mother-infant pairs at Health Centres in the Aosta Region of Italy. Infants aged 2-4 months were randomly allocated to a singing intervention group or to a control group whose injections were administered following standard practice. Pre- and post-immunisation pain was blindly assessed using the Modified Behavioural Pain Scale, and mother-infant proximity indexes were assigned based on muted video-tracks. RESULTS: When assessed for pain, the infants in the maternal singing group were assigned significantly lower movement indexes (p = 0.032) and marginally significantly lower cry indexes (p = 0.076). A higher frequency of mother-to-infant gaze (p < 0.005) was observed in the singing group dyads. Finally, the intervention group mothers' self-perceived ease in singing was correlated with their previous singing experience and with lower anxiety following the vaccination procedure (p < 0.05). CONCLUSION: Maternal singing during immunisation procedures benefits both mothers and babies. The practice of singing is a biologically rooted and adaptive form of intuitive parental communication that should be encouraged, especially in at-risk populations.

Preterm infants show an atypical processing of the mother's voice.

To understand the consequences of prematurity on language perception, it is fundamental to determine how atypical early sensory experience affects brain development. At term equivalent age, ten preterm and ten full-term newborns underwent high-density EEG during mother or stranger speech presentation, in the forward or backward order. A general group effect terms > preterms is evident in the theta frequency band, in the left temporal area, with preterms showing significant activation for strangers' and terms for the mother's voice. A significant group contrast in the low and high theta in the right temporal regions indicates higher activations for the stranger's voice in preterms. Finally, only full terms presented a late gamma band increase for the maternal voice, indicating a more mature brain response. EEG time-frequency analysis demonstrate that preterm infants are selectively responsive to stranger voices in both temporal hemispheres, and that they lack selective brain responses to their mother's forward voice.

Musical memories in newborns: A resting-state functional connectivity study.

Music is known to induce emotions and activate associated memories, including musical memories. In adults, it is well known that music activates both working memory and limbic networks. We have recently discovered that as early as during the newborn period, familiar music is processed differently from unfamiliar music. The present study evaluates music listening effects at the brain level in newborns, by exploring the impact of familiar or first-time music listening on the subsequent resting-state functional connectivity in the brain. Using a connectome-based framework, we describe resting-state functional connectivity (RS-FC) modulation after music listening in three groups of newborn infants, in preterm infants exposed to music during their neonatal-intensive-care-unit (NICU) stay, in control preterm, and full-term infants. We observed modulation of the RS-FC between brain regions known to be implicated in music and emotions processing, immediately following music listening in all newborn infants. In the music exposed group, we found increased RS-FC between brain regions known to be implicated in familiar and emotionally arousing music and multisensory processing, and therefore implying memory retrieval and associative memory. We demonstrate a positive correlation between the occurrence of the prior music exposure and increased RS-FC in brain regions implicated in multisensory and emotional processing, indicating strong engagement of musical memories; and a negative correlation with the Default Mode Network, indicating disengagement due to the aforementioned cognitive processing. Our results describe the modulatory effect of music listening on brain RS-FC that can be linked to brain correlates of musical memory engrams in preterm infants.

Systematic review shows the benefits of involving the fathers of preterm infants in early interventions in neonatal intensive care units.

AIM: This review identifies interventions involving the fathers of preterm infants that have been tested in neonatal intensive care units (NICU). It examines their effects on the fathers and infants and highlights any differences between fathers and mothers who took part in the same interventions. METHODS: A systematic search was performed in English from 1995 to 1 September 2020, using the CINAHL, Cochrane Central Register of Controlled Trials, Embase, PubMed and PsycINFO databases. We examined 14 peer-reviewed studies that investigated NICU interventions involving 478 fathers, whose 511 infants were born before 37 weeks of gestation. These included empirical studies with clinical outcomes. RESULTS: Studies on fathers' interventions in NICUs were limited and mainly restricted to basic skin-to-skin contact or tactile interventions. The interventions had similar general positive effects on mothers and fathers when it came to infant physiological and behavioural reactions. There was also evidence of a positive effect on the fathers, including their mental health. CONCLUSION: Including fathers as active partners in the care of their preterm newborn infants produced good outcomes for both of them. Further research is needed to develop new, multimodal and interactive interventions that provide fathers with positive contact with their preterm infants.

Early vocal contact and music in the NICU: new insights into preventive interventions.

It is now clearly established that the environment and the sensory stimuli, particularly during the perinatal period, have an impact on infant's development. During the last trimester of gestation, activity-dependent plasticity shapes the fetal brain, and prematurity has been shown to alter the typical developmental trajectories. In this delicate period, preventive interventions aiming at modulating these developmental trajectories through activity-inducing interventions are currently underway to be tested. The purpose of this review paper is to describe the potentialities of early vocal contact and music on the preterm infant's brain development, and their potential beneficial effect on early development. Scientific evidence supports a behavioral orientation of the newborn to organized sounds, such as those of voice and music, and recent neuroimaging studies further confirm full cerebral processing of music as multisensory stimuli. However, the impact of long-term effects of music exposure and early vocal contact on preterm infants' long-term neurodevelopment needs be further investigated. To conclude, it is necessary to establish the neuroscientific bases of the early perception and the long-term effects of music and early vocal contact on the premature newborns' development. Scientific projects are currently on the way to fill this gap in knowledge.

Changes in the vocal qualities of mothers and fathers are related to preterm infant's behavioural states.

AIM: Little is known about infant-directed speech addressed to preterm infants. The current study investigated the association between changes in preterm infant behavioural states and acoustical qualities of both maternal and paternal infant-directed speech. METHODS: The mothers and fathers of 11 preterm infants participated in the study. Parents in turn were asked to talk freely to their infant over a 5-minute period. A total of 72 audio sequences were selected and analysed as a function of the behavioural states. RESULTS: Acoustic analysis showed that the vocal qualities of both fathers' and mothers' speech were influenced by infant behaviour. Parental infant-directed speech was characterised by higher loudness and spectral related parameters when preterm infants were sleeping, or transiting from one state to another, than when they were awake. Furthermore, loudness and spectral flux were higher in maternal speech than in paternal speech and fathers used higher pitch, jitter and shimmer when they saw their preterm infant in an awake state, demonstrating that alertness in infants modulates the father's voice. CONCLUSION: More research is needed to know whether other social partners' vocal qualities may also be related to infant behavioural state as such findings would have implications for clinical practice.

Language in Preterm Born Children: Atypical Development and Effects of Early Interventions on Neuroplasticity.

Predicting language performances after preterm birth is challenging. It is described in the literature that early exposure to the extrauterine environment can be either detrimental or advantageous for neurodevelopment. However, the emphasis mostly lies on the fact that preterm birth may have an unfavorable effect on numerous aspects of development such as cognition, language, and behavior. Various studies reported atypical language development in preterm born children in the preschool years but also in school-aged children and adolescents. This review gives an overview of the course of language development and examines how prematurity can lead to atypical linguistic performances. In this paper, we mainly focus on environmental and neurophysiological factors influencing preterm infant neuroplasticity with potential short- and long-term effects on language development. Further research, however, should focus on examining the possible benefits that early exposure might entail.

Exposure to human voices has beneficial effects on preterm infants in the neonatal intensive care unit.

We reviewed the literature up to March 2016 on the effects of nonmaternal voices on preterm infants' clinical outcomes. Of the 11 studies that met the inclusion criteria, 10 focused on short-term outcomes and one looked at long-term effects. The studies mainly showed that vocal stimuli increased preterm infants' stability in terms of heart rate, respiratory rate, oxygen saturation and behavioural measures. Improvements in feeding skills were also reported. The methods and the measures used in the studies were heterogeneous, making it difficult to draw reliable conclusions. CONCLUSION: Vocal stimuli increased preterm infants' stability, but further studies are needed.

Systematic review of maternal voice interventions demonstrates increased stability in preterm infants.

We systematically reviewed how effectively maternal voice interventions supported the clinical outcomes and development of preterm infants. A total of 512 preterm infants were included in 15 studies with different designs, from January 2000 to July 2015. Live and recorded maternal voice interventions were associated with the physiologic and behavioural stabilisation of preterm infants, with fewer cardiorespiratory events, but the evidence was insufficient to evaluate the long-term effects. Well-defined determinants and clear setting conditions are needed for such interventions. CONCLUSION: Further research that investigates the long-term efficacy and effects of live maternal voices on preterm infant development is needed.

Live maternal speech and singing have beneficial effects on hospitalized preterm infants.

AIM: To study the effects of live maternal speaking and singing on physiological parameters of preterm infants in the NICU and to test the hypothesis that vocal stimulation can have differential effects on preterm infants at a behavioural level. METHODS: Eighteen mothers spoke and sang to their medically stable preterm infants in their incubators over 6 days, between 1 and 2 pm. Heart rate (HR), oxygen saturation (OxSat), number of critical events (hypoxemia, bradycardia and apnoea) and change in behavioural state were measured. RESULTS: Comparisons of periods with and without maternal vocal stimulation revealed significantly greater oxygen saturation level and heart rate and significantly fewer negative critical events (p < 0.0001) when the mother was speaking and singing. Unexpected findings were the comparable effects of maternal talk and singing on infant physiological parameters and the differential ones on infant behavioural state. CONCLUSION: A renewed connection to the mother's voice can be an important and significant experience for preterm infants. Exposure to maternal speech and singing shows significant early beneficial effects on physiological state, such as oxygen saturation levels, number of critical events and prevalence of calm alert state. These findings have implications for NICU interventions, encouraging maternal interaction with their medically stable preterm infants.

Oxytocin Levels Increase and Anxiety Decreases in Mothers Who Sing and Talk to Their Premature Infants during a Painful Procedure.

(1) Background: Preterm infants spend their first weeks of life in the hospital partially separated from their parents and subjected to frequent potentially painful clinical procedures. Previous research has found that early vocal contact reduces infant pain perception while simultaneously increasing oxytocin (OXT) levels. The current study aims to assess the effect of maternal singing and speaking on mothers. (2) Methods: During a painful procedure over two days, twenty preterm infants were randomly exposed to their mother's live voice (speaking or singing). Maternal OXT levels were measured twice: before and after singing, as well as before and after speaking. The anxiety and resilience responses of mothers were studied before and after the two-day interventions, regardless of the speaking/singing condition. OXT levels in mothers increased in response to both singing and speech. Concurrently, anxiety levels decreased, but no significant effects on maternal resilience were found. (3) Conclusions: OXT could be identified as a key mechanism for anxiety regulation in parents, even in sensitive care situations, such as when their infant is in pain. Active involvement of parents in the care of their preterm infants can have a positive effect on their anxiety as well as potential benefits to their sensitivity and care abilities through OXT.

Maternal Voice and Tactile Stimulation Modulate Oxytocin in Mothers of Hospitalized Preterm Infants: A Randomized Crossover Trial.

Prematurity is a major risk factor for perinatal stress and neonatal complications leading to systemic inflammation and abnormal mother-infant interactions. Oxytocin (OT) is a neuropeptide regulating the inflammatory response and promoting mother-infant bonding. The release of this hormone might be influenced by either vocal or tactile stimulation. The main objective of the current randomized, crossover, clinical trial was to assess the salivary OT/cortisol balance in mothers following the exposure of their baby born preterm to two types of sensorial interventions: maternal voice without or with contingent tactile stimulation provided by the mother to her infant. Among the 26 mothers enrolled, maternal voice intervention alone had no effect on OT and cortisol levels in the mothers, but when associated with tactile stimulation, it induced a significant increase in maternal saliva oxytocin (38.26 ± 30.26 pg/mL before vs 53.91 ± 48.84 pg/mL after, p = 0.02), particularly in the mothers who delivered a female neonate. Maternal voice intervention induced a significant reduction in cortisol and an increase in OT levels in mothers when the maternal voice with a tactile stimulation intervention was performed first. In conclusion, exposure to the maternal voice with a contingent tactile stimulation was associated with subtle changes in the maternal hormonal balance between OT and cortisol. These findings need to be confirmed in a larger sample size and may ultimately guide caregivers in providing the best intervention to reduce parental stress following preterm delivery.

Maternal Singing but Not Speech Enhances Vagal Activity in Preterm Infants during Hospitalization: Preliminary Results.

BACKGROUND: Early parental interventions in the Neonatal Intensive Care Units (NICUs) have beneficial effects on preterm infants' short and long-term outcomes. The aim of this study was to investigate the effects of Early Vocal Contact (EVC)-singing and speaking-on preterm infants' vagal activity and autonomic nervous system (ANS) maturation. METHODS: In this multi-center randomized clinical trial, twenty-four stable preterm infants, born at 25-32 weeks gestational age, were randomized to either the EVC group or control group, where mothers did not interact with the babies but observed their behavior. Heart Rate Variability (HRV) was acquired before intervention (pre-condition), during vocal contact, and after it (post condition). RESULTS: No significant effect of the vocal contact, singing and speaking, was found in HRV when the intervention group was compared to the control group. However, a significant difference between the singing and the pre and post conditions, respectively, preceding and following the singing intervention, was found in the Low and High Frequency power nu, and in the low/high frequency features (p = 0.037). By contrast, no significant effect of the speaking was found. CONCLUSIONS: Maternal singing, but not speaking, enhances preterm infants' vagal activity in the short-term, thus improving the ANS stability. Future analyses will investigate the effect of enhanced vagal activity on short and long-term developmental outcomes of preterm infants in the NICU.

Parental Perception of Vocal Contact with Preterm Infants: Communicative Musicality in the Neonatal Intensive Care Unit.

In this study, we evaluate mothers' subjective experience of speaking and singing to their infants while they are in their incubators. We also discuss the relevance of the theoretical framework of Communicative Musicality for identifying the underlying mechanisms that may help explain its beneficial effects, both for parents and infants. Nineteen mothers talked and sung to their stable preterm infants in the incubators, for 5 min each, in three sessions over a period of 6 days. After each session, mothers were asked to assess in a self-report questionnaire the ease and the effectiveness of addressing their infants by speaking and singing and their prior musical experience. Perceived ease and effectiveness in communication were found to increase progressively from one session to the next. Mothers rated the speech to be increasingly more effective. This intuitive mean of interaction between parents and infants could be encouraged and supported by the nurses and the medical staff. Furthermore, individual musical experience affects perceived ease of communicating vocally with infants after a premature birth and should thus be encouraged during pregnancy.

Maternal speech decreases pain scores and increases oxytocin levels in preterm infants during painful procedures.

Preterm infants undergo early separation from parents and are exposed to frequent painful clinical procedures, with resultant short- and long-term effects on their neurodevelopment. We aimed to establish whether the mother's voice could provide an effective and safe analgesia for preterm infants and whether endogenous oxytocin (OXT) could be linked to pain modulation. Twenty preterm infants were exposed to three conditions-mother's live voice (speaking or singing) and standard care-in random order during a painful procedure. OXT levels (pg/mL) in saliva and plasma cortisol levels were quantified, and the Premature Infant Pain Profile (PIPP) was blindly coded by trained psychologists. During the mother's live voice, PIPP scores significantly decreased, with a concomitant increase in OXT levels over baseline. The effect on pain perception was marginally significant for singing. No effects on cortisol levels were found. The mother's live voice modulated preterm infants' pain indicators. Endogenous OXT released during vocal contact is a promising protective mechanism during early painful interventions in at-risk populations.

Effects of Early Vocal Contact in the Neonatal Intensive Care Unit: Study Protocol for a Multi-Centre, Randomised Clinical Trial.

Preterm infants are at risk for developing altered trajectories of cognitive, social, and linguistic competences compared to a term population. This is mainly due to medical and environmental factors, as they are exposed to an atypical auditory environment and simultaneously, long periods of early separation from their parents. The short-term effects of early vocal contact (EVC) on an infant's early stability have been investigated. However, there is limited evidence of its impact on the infant's autonomic nervous system maturation, as indexed by heart rate variability, and its long-term impact on infant neurodevelopment. Our multi-centric study aims to investigate the effects of EVC on a preterm infant's physiology, neurobehaviour, and development. Eighty stable preterm infants, born at 25-32 weeks and 6 days gestational age, without specific abnormalities, will be enrolled and randomised to either an intervention or control group. The intervention group will receive EVC, where mothers will talk and sing to their infants for 10 min three times per week for 2 weeks. Mothers in the control group will be encouraged to spend the same amount of time next to the incubator and observe the infant's behaviour through a standard cluster of indicators. Infants will be assessed at baseline; the end of the intervention; term equivalent age; and 3, 6, 12, and 24 months corrected age, with a battery of physiological, neurobehavioral, and developmental measures. Early interventions in the neonatal intensive care unit have demonstrated effects on the neurodevelopment of preterm infants, thereby lowering the negative long-term effects of an atypical auditory and interactional environment. Our proposed study will provide new insight into mother-infant early contact as a protective intervention against the sequelae of prematurity during this sensitive period of development. Early intervention, such as EVC, is intuitive and easy to implement in the daily care of preterm infants. However, its long-term effects on infant neurodevelopment and maternal sensitivity and stress are still unclear. Trial Registration: NCT04759573, retrospectively registered, 17 February 2021.